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Objective To investigate the correlation between the ratio of lesion volume to uterine volume (T/U), the expression levels of Ki-67 and p16 proteins in lesion tissue, and the recurrence risk of endometrial cancer. Methods A total of 150 patients diagnosed with endometrial carcinoma through pathological examination at Qiandongnan Prefecture People's Hospital were enrolled for follow-up observation. Among them, 28 patients experienced recurrence after a 2-year follow-up period, while 122 patients remained recurrence-free. The expression differences of Ki-67 protein and p16 protein in T/U and lesion tissues during surgery were compared between the two groups. Furthermore, these indexes were analyzed based on different pathological features, and the variation in relapse-free survival time was assessed among patients with distinct T/U status as well as Ki-67 and p16 protein expressions. Results The T/U value and the positive expression rate of Ki-67 protein were significantly higher in the relapsed group compared to the non-relapsed group, while the positive expression rate of p16 protein was significantly lower in the relapsed group (P < 0.05). Additionally, patients with T/U ≥ 0.18 had a significantly higher proportion of stage Ⅲ patients and patients with low histological differentiation compared to those with T/U < 0.18（P < 0.05). Furthermore, patients with positive expression of Ki-67 protein exhibited a significantly higher proportion of stage Ⅲ patients, patients with low histological differentiation, and lymph node metastasis compared to those with negative expression of Ki-67 protein (P < 0.05). The proportion of stage Ⅲ patients exhibiting positive p16 protein expression, low histological differentiation, and lymph node metastasis was significantly lower compared to those with negative p16 protein expression (P < 0.05). Patients with endometrial cancer having a T/U ≥ 0.18 experienced shorter recurrence-free survival time 2 years post-surgery in comparison to patients with T/U < 0.18（χ² = 6.962, P = 0.008). Patients displaying positive Ki-67 expression had a shorter recurrence-free survival time 2 years after surgery than those with negative Ki-67 expression (χ² = 4.815, P = 0.028). The recurrence-free survival time 2 years after surgery for patients expressing p16 protein positively was longer than that for patients expressing it negatively (χ² = 4.279, P = 0.039). The presence of FIGO stage Ⅲ, lymph node metastasis, depth of myographic invasion ≥1/2, T/U value ≥ 0.18, and positive expression of Ki-67 protein were identified as significant risk factors for postoperative recurrence in endometrial cancer (P < 0.05). Conversely, the positive expression of p16 protein was found to be a protective factor against recurrence in endometrial carcinoma following surgery (P < 0.05). Conclusion The expression of T/U, Ki-67 protein, and p16 protein in endometrial cancer patients is associated with tumor progression and may augment the risk of postoperative recurrence. [ABSTRACT FROM AUTHOR]

Background: Ancillary immunohistochemistry testing for p16 loss has been proposed as a diagnostic tool for melanoma, but its accuracy remains uncertain. Methods: A systematic review and meta‐analysis were conducted on 26 studies involving 979 melanomas and 974 nevi. Results: Through bivariate analysis of data across all cut‐off values, the sensitivity and specificity were calculated to be 0.55 (95% confidence interval [CI]: 0.38, 0.70) and 0.85 (95% CI: 0.70, 0.94), respectively. Summary estimates of diagnostic accuracy fell below recommended thresholds for effective tests, but subgroup analysis suggested that p16 loss could aid in diagnosing ambiguous lesions as melanoma in certain scenarios. However, the presence of p16 expression in these contexts does not definitively rule out melanoma. The findings were limited by underpowered exploratory study designs at risk for bias in patient selection and test interpretation. Conclusions: While the use of p16 immunohistochemistry for detecting melanoma is not universally reliable, it may serve as a confirmatory test in differential diagnoses involving common, congenital, acral, Spitz, and deep penetrating nevi. Nevertheless, further studies are needed to validate its utility. Until then, the application of p16 immunohistochemistry in melanoma diagnosis should be regarded as experimental. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect p16 protein combined with HPV-DNA and TCT in screening cervical cancer lesions. Methods: A retrospective analysis was conducted on 3952 suspected patients who visited a women's and children's health hospital in a certain area of Guangzhou from February 2023 to December 2023. Parallel p16 protein detection, HPV-DNA screening, Thin-prep cytologic test(TCT), and cervical cancer histopathological section (HE) identification were performed. The correlation between p16 protein immunohistochemistry, HPV-DNA typing, and TCT test results in different age groups of women was analyzed and compared. Results: The positive rate of p16 protein detection tended to increase with the increase in HPV-DNA screening (the difference was statistically significant, P<0.05). p16 protein detection tended to increase with the grading of TCT diagnosis results from NILM to ASC-US, ASC-H, LSIL, HSIL, and SCC groups (the difference was statistically significant, P<0.05). p16 protein detection tended to increase with the grading of cervical cancer histopathological sections by HE staining (the difference was statistically significant, P<0.05). The positive rate of p16 protein detection was closely related to patient age; among the 3952 women, 1836 were HPV-DNA screening positive, with a positive rate of approximately 46.46%; 1528 were TCT positive, with a positive rate of approximately 38.66%; grouped by age, the onset age tended to increase after 30 years old, peaked at 41-50 years old, and decreased after 60 years old, showed an upward and downward parabolic trend with age; the onset of cervical cancer also showed a trend of younger age. Conclusion: The combination of p16 protein, HPV-DNA, and TCT improved the accuracy of cervical cancer and precancerous lesion screening. [ABSTRACT FROM AUTHOR]

Objective: To understand the characteristics of cervical lymph node metastasis in Oropharyngeal Squamous Cell Carcinoma (OPSCC) patients, explore the risk factors for lymph node metastasis, and its impact on prognosis. Methods: Retrospective cohort study. Statistical analysis of the relationship between various clinicopathological factors and lymph node involvement, as well as the independent risk factors affecting lymph node metastasis and their impact on prognosis. Results: The cervical lymph node metastasis rate in this group was 89.2%, with the palatine tonsils and base of the tongue more prone to cervical lymph node metastasis (p = 0.007); lower pathological differentiation of OPSCC was more likely to develop cervical lymph node metastasis (p = 0.017). The P16 protein positive rate in this group was 58.8%. P16 protein expression did not affect the incidence rate of cervical lymph node metastasis in OPSCC (p = 1.000) but influenced the risk of multiple lymph node metastases (p = 0.011) and was a risk factor affecting the prognosis of OPSCC (p = 0.003). However, the lymph node metastasis status did not affect the survival time of OPSCC patients. Conclusion: In the Shanxi region of China, HPV-related OPSCC accounts for a higher proportion; OPSCC has a high rate of cervical lymph node metastasis, but lymph node metastasis does not significantly increase the mortality risk of OPSCC patients, which may be related to the unique characteristics of HPV-related OPSCC. Level of Evidence Ⅳ: Retrospective cohort study.

Human papillomavirus (HPV) is an oncogenic DNA virus that plays a role in different cancer types. The aim of this study was to detect the prevalence and types of HPV and its relation with p16, EGFR and clinical findings in lung cancer. HPV and EGFR detection and genotyping of HPV were performed by polymerase chain reaction (PCR) and p16 by immunohistochemistry. Fifty lung cancer patients and seven patients with non-neoplastic lung disease were enrolled in this study. HPV was positive in 78% (39/50) of lung cancer cases. HPV 51 was the most frequent type, followed by HPV 16. Moreover, p16 was positive in 24% (12/50) of the cancer patients, and all of these patients were HPV-positive, while 27 HPV-positive patients showed no p16 expression. There was no relationship between HPV infection and p16 (p = 0.05), gender (p = 0.42), age (p = 0.38), or smoking history (p = 0.68). Although not statistically significant, the HPV prevalence was found to be higher in cancer patients compared to non-neoplastic patients. The prevalence of HPV in lung cancer varies across different studies, which may be due to differences in the detection methods, number of patients, geographic regions, and vaccination status. Further studies are necessary to understand the role of HPV in lung cancer pathogenesis. [ABSTRACT FROM AUTHOR]

Testin is a protein expressed in normal human tissues, being responsible, with other cytoskeleton proteins, for the proper functioning of cell–cell junction areas and focal adhesion plaques. It takes part in the regulation of actin filament changes during cell spreading and motility. Loss of heterozygosity in the testin-encoding gene results in altered protein expression in many malignancies, as partly described for cervical cancer. The aim of our study was the assessment of the immunohistochemical (IHC) expression of testin in cervical cancer and its analysis in regard to clinical data as well the expression of the Ki-67 antigen and p16 protein. Moreover, testin expression was assessed by Western blot (WB) in commercially available cell lines. The IHC analysis disclosed that the expression of testin inversely correlated with p16 (r = −0.2104, p < 0.0465) and Ki-67 expression (r = −0.2359, p < 0.0278). Moreover, weaker testin expression was observed in cancer cases vs. control ones (p < 0.0113). The WB analysis of testin expression in the cervical cancer cell lines corresponded to the IHC results and showed a weaker expression compared to that in the control cell line. When we compared the expression of testin in cervical cancer cell lines, we found a weaker expression in HPV-negative cell lines. In summary, we found that the intensity of testin expression and the number of positive cells inversely correlated with the expression of Ki-67 (a marker of proliferation) and p16 (a marker of cell cycle dysregulation). This study shows that the combined assessment of testin, Ki-67 and p16 expression may improve cervical cancer diagnostics.

The longstanding phrase, traditional risk factors like—smoking, tobacco and alcohol are the only causative agents of oral and oropharyngeal squamous cell carcinoma (SCC) is changing now. Etiological divergence is taking place which we have to know to reach upon an exact cause of the disease. Human papilloma virus (HPV) infection is a well-established cause of oral cancer. Escalating incidence of HPV associated cancer has a strong impact on its management. So, a concern clinician needs to get aware for it. Among various types of HPV, HPV-16 is more frequently associated with oral cancers. HPV detection will become a game changer in management of oral cancers. HPV infection and p16 protein expression has a strong and consistent correlation. Therefore, immunohistochemical analysis of p16 protein can be a surrogate biomarker in high risk groups. This hospital based prospective observational study recruited 180 subjects of oral and oropharyngeal SCC. We underwent immunohistochemical analysis of p16 in biopsy specimen of subjects and studied HPV status and associated environmental, clinical and behavioral factors. We observed 9.4% (17/180) incidence of p16 positivity with female predominance. Our observations showed that its prevalence was higher in urban patients who were non tobacco users, had sexually transmitted disease, early stage (T1–T2), poorly differentiated SCC with nodal metastasis. We conclude that keeping in mind HPV as a cause of oral and oropharyngeal SCC, p16 should be use as a biomarker for its detection in high risk cases. [ABSTRACT FROM AUTHOR]

Abstract Background According to the 2006 American Society for Colposcopy and Cervical Pathology guidelines, positive CIN2 p16 in women over the age of 25 should be managed with excisional treatment. However, excisional treatment is associated with physical, psychological and obstetric morbidity and can have a negative impact on sexual function. In our study we sought to identify a clear management strategy, addressing the impact of routine use of p16 immunohistochemistry in this population and identify appropriate criteria for patient selection with the aim of reducing over-treatment. Method We studied the medical records of 130 patients who had undergone laser therapy for CIN2. Each patient underwent colposcopy, biopsy and HPV test and were tested for p16 protein,. Patients were divided based on HPV infection into: single infections, multiple infections. All patients underwent ZTA laser therapy with follow-up (2-year follow-up). Statistical analysis Contingency tables were created to evaluate the correlation between single, multiple and CIN2+ infections. Values with p

Objective: To determine expression of p16 mutant protein and ki67 in cutaneous and non-cutaneous melanoma. Study Design: Cross sectional study. Place and Duration of Study: Armed Forces Institute of Pathology, Rawalpindi, from July 2017 to July 2018. Methodology: All cases of melanoma diagnosed by histopathological examination were included. P16 and ki67 antibodies for immunohistochemical studies were applied in all cases. Patient’s gender, age, tumor site and results of immunohistochemical (IHC) stains were noted. Results: A total number of 40 cases of melanoma were studied. It was more common in males 28 (70%) than females 12(30%). Mean age of presentation was 51.1 ± 1.17 years. Most of the patients i.e., 25 (62.5%), were in age group above 50 years, Cutaneous melanoma was the commonest type being 22 (55%), followed by ocular melanoma being 14 (35%) and mucosal melanoma 4 (10%). The immunohistochemical staining for p16 was positive in all cases (100%). Ki67 proliferative index was high in most cases 34 (85%). It was low in the rest of cases being 6 (15%). Conclusion: Melanoma was found more common in males in the age group above 50 years. Cutaneous melanoma was the most common type. There was strong correlation between p16 and ki67 expression. P16 was seen in all cases. High ki67 was seen in 85% of cases.

Introduction: Cervical cancer is the 3rd most common cancer among women worldwide. p16 biomarker is the surrogate marker in cervical cancer and can be detected by Immunohistochemistry (IHC). Aim: To evaluate the association of IHC p16INK4a expression in tissue sections and Enzyme-linked Immunosorbent Assay (ELISA) p16INK4a protein in plasma of paired samples in Squamous Cell Carcinoma (SCC) of uterine cervix. Materials and Methods: This laboratory-based observational, pilot study was conducted at tertiary care centre of Sri Devaraj Urs Medical College in South India from June 2020 to May 2021. Total 17 new cases of SCC of cervix diagnosed by histopathology were considered for the study. The cases were staged as per International Federation of Gynaecology and Obstetrics (FIGO) staging system and classified by histopathology as keratinising and non keratinising types. IHC p16INK4a evaluation was done on tissue sections and classified as block positivity, ambiguity and negative. ELISA p16INK4a estimation was done using plasma from Dipotassium Ethylenediaminetetraacetic Acid (K2-EDTA) blood sample of same cases. Statistical analysis was done using Statistical Package for the Social Sciences (SPSS) version 22.0 software. Results: The age ranged from 30-80 years with mean of 54.3±12.0 years. Plasma ELISA p16INK4a level ranged from 3.4-19.6 ng/mL with a mean of 7.2±2.35 ng/mL in SCC of cervix. The plasma p16INK4a ELISA levels of 5.1 to 6.2 ng/mL, 6.0 to 6.6 ng/mL and 5.5 to 9.7 ng/mL predicts negative, ambiguity and block positivity of IHC p16INK4a expression respectively in corresponding tissue biopsy. Plasma ELISA p16INK4a levels were maximum in Non Keratinising Squamous Cell Carcinoma (NKSCC) followed by Well Differentiated Squamous Cell Carcinoma (WDSCC), Moderately Differentiated Squamous Cell Carcinoma (MDSCC) and Poorly Differentiated Squamous Cell Carcinoma (PDSCC). Conclusion: The plasma ELISA p16INK4a levels and IHC p16INK4a expression were maximum in higher disease stage compared to lower stage. This was a pilot study to evaluate the association between tissue IHC p16 expression and plasma ELISA p16 levels. Further study has to be done on larger study population with standardised procedure to prove the hypothesis.

The tumor suppressor p16 protein is an endogenous CDK4/6 inhibitor. Inactivation of its encoding gene is found in nearly half of human cancers. Restoration of p16 function via adenovirus-based gene delivery has been shown to be effective in suppressing aberrant cell growth in many types of cancer, however, the potential risk of insertional mutagenesis in genomic DNA remains a major concern. Thus, there has been great interest in developing efficient strategies to directly deliver proteins into cells as an alternative that can avoid such safety concerns while achieving a comparable therapeutic effect. Nevertheless, intracellular delivery of protein therapeutics remains a challenge. Our group has recently developed a protein delivery platform based on an engineered Pos3Aa protein that forms sub-micrometer-sized crystals in Bacillus thuringiensis cells. In this report, we describe the further development of this platform (Pos3AaTM) via rationally designed site-directed mutagenesis, and its resultant potency for the delivery of cargo proteins into cells. Pos3AaTM-based fusion protein crystals are shown to exhibit improved release of their cargo proteins as demonstrated using a model mCherry protein. Importantly, this Pos3AaTM platform is able to mediate the efficient intracellular delivery of p16 protein with significant endosomal escape, resulting in p16-mediated inhibition of CDK4/6 kinase activity and Rb phosphorylation, and as a consequence, significant cell cycle arrest and cell growth inhibition. These results validate the ability of these improved Pos3AaTM crystals to mediate enhanced cytosolic protein delivery and highlight the potential of using protein therapeutics as selective CDK4/6 inhibitors for cancer therapy. Cytosolic delivery of bioactive therapeutic proteins capable of eliciting therapeutic benefit remains a significant challenge. We have previously developed a protein delivery platform based on engineered Pos3Aa protein crystals with excellent cell-permeability and endosomal escape properties. In this report, we describe the rational design of an improved Pos3Aa triple mutant (Pos3AaTM) with enhanced cargo release. We demonstrate that Pos3AaTM-mCherry-p16 fusion crystals can efficiently deliver p16 protein, a CDK4/6 inhibitor frequently inactivated in human cancers, into p16-deficient UM-SCC-22A cells, where it promotes significant G1 cell cycle arrest and cell growth inhibition. These results highlight the ability of the Pos3AaTM platform to promote potent cytosolic delivery of protein therapeutics, and the efficacy of p16 protein delivery as an effective strategy for treating cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Inclusion of depth of invasion (DOI) and a separate classification for human papillomavirus (HPV)-associated Oropharyngeal Cancers (OPCs) are two of the many major changes in the 8th edition of the American Joint Committee on Cancer staging system. After more than 2 years of implementation, the authors found the need to evaluate if the Indian clinicians found it feasible to apply the system in their practice and if the same has influenced their decision-making. Methods: The survey was done in the form of a questionnaire which was distributed personally and via the internet to 100 clinicians. Seventy-two clinicians responded to the questionnaire. The results were analyzed and frequency distribution was computed. Results: Eighty-three percent of the clinicians experienced that palpation of the tumour was not a reliable method to determine the DOI. The common issues stated by the clinicians were difficulty in assessing DOI in certain subsites of the oral cavity (most commonly retromolar trigone–83%), inability to determine DOI in patients with trismus, and inability to correlate pathological and clinical DOI. Thirteen percent of the clinicians did not rely on radiological tools for measuring the DOI. Seventy percent of the clinicians did not perform a P16 assay for patients with oropharyngeal cancers. Fifty percent of the clinicians preferred chemoradiotherapy for early HPV positive oropharyngeal cancers. Discussion: Based on the results of the survey, the authors recommend a need for more interpretative guidelines and methods for determining the DOI. The authors also emphasize the need for determining HPV status for all oropharyngeal carcinomas. [ABSTRACT FROM AUTHOR]

Introduction: P16 is an independent and reliable surrogate for the detection of human papillomavirus (HPV) in oral squamous cell carcinoma (OSCC). The aim of this study was to assess the P16 expression as a marker for HPV infection in OSCC and its impact on the treatment outcome. Methods and Materials: A cross-sectional study was conducted on patients with a definite diagnosis of OSCC. Patients were assigned into two groups with and without recurrence or metastasis. Tumour resection was performed in the same manner for all patients. P16 expression was evaluated by immunohistochemical staining. Independent t-test and Chi-square tests were used to find significant differences in age, gender, stage of the disease, tumour size, lymph node involvement, and P16 expression between the two groups. Results: Of 50 patients, 37 did not show any recurrence or metastasis (group 1), while 13 had a relapse (group 2). There was no significant difference for age, gender distribution, stage of the disease, or lymph node involvement between the two groups (P > 0.05). A significant difference in tumour size was noted between the two groups (P = 0.001). The mean expression of P16 was 38.92 ± 24.36 in group 1 and 51.54 ± 33.63 in group 2. No significant difference was found between the two groups for the mean expression of P16 (P = 0.23). Discussion: A review of the recent literature revealed that the HPV role in OSCC treatment is controversial. According to the results of this study, there was no significant difference in terms of P16 expression between OSCC patients with and without recurrence or metastasis. [ABSTRACT FROM AUTHOR]

Objective This study aimed at confirming the alteration of circulating anti-p16 immunoglobulin G (IgG) levels in hepatocellular carcinoma (HCC). Methods An in-house-developed enzyme-linked immunosorbent assay was used for determining plasma IgG antibodies against p16-derived antigens in 122 HCC patients and 134 healthy controls. Results Plasma anti-p16 IgG levels were significantly higher in HCC patients than in the controls (Z =  3.51, P =  0.0004), with no difference between males and females. A trend of increasing plasma anti-p16 IgG levels was associated with increasing HCC stage, with group 3 patients having the highest anti-p16 IgG levels (Z =  3.38, P =  0.0008). Group 3 exhibited the best sensitivity (19.6%) and specificity (95%) for plasma anti-p16 IgG detection, with an area under the receiver operating characteristic curve of 0.659 (95% confidence interval, 0.564–0.754). Conclusion Circulating IgG antibody to p16 protein might be a useful biomarker for HCC prognosis assessment rather than for early malignancy diagnosis. [ABSTRACT FROM AUTHOR]

Colorectal carcinoma is one of the most frequent human malignant neoplasms. Besides the most common histological types, colorectal adenosquamous carcinoma is very rare, being microscopically constituted by tumoural glandular and squamous components. The diagnosis of primary colon adenosquamous carcinoma requires the exclusion of a metastatic squamous cell carcinoma and the extension of a primary squamous cell carcinoma from the anal–rectum junction. We report a case of primary adenosquamous carcinoma of the ascending colon in a 62-year-old Caucasian man affected by long-standing ulcerative colitis. Peritumoural lymph nodes and distant metastasis were present. We reported also a diffuse signet-ring mucinous component, which has not been previously observed. Moreover, we investigated microsatellite and all-RAS/B-RAF status, p16 and p53 protein expression, and the molecular presence of human papillomavirus DNA in all the morphologically distinct components, in order to suggest pathogenetic factors influencing the aggressive prognosis of colon adenosquamous carcinoma. [ABSTRACT FROM AUTHOR]

Objective: To determine expression of p16 mutant protein and ki67 in cutaneous and non-cutaneous melanoma. Study Design: Cross sectional study. Place and Duration of Study: Armed Forces Institute of Pathology, Rawalpindi, from July 2017 to July 2018. Methodology: All cases of melanoma diagnosed by histopathological examination were included. P16 and ki67 antibodies for immunohistochemical studies were applied in all cases. Patient’s gender, age, tumor site and results of immunohistochemical (IHC) stains were noted. Results: A total number of 40 cases of melanoma were studied. It was more common in males 28 (70%) than females 12(30%). Mean age of presentation was 51.1 ± 1.17 years. Most of the patients i.e., 25 (62.5%), were in age group above 50 years, Cutaneous melanoma was the commonest type being 22 (55%), followed by ocular melanoma being 14 (35%) and mucosal melanoma 4 (10%). The immunohistochemical staining for p16 was positive in all cases (100%). Ki67 proliferative index was high in most cases 34 (85%). It was low in the rest of cases being 6 (15%). Conclusion: Melanoma was found more common in males in the age group above 50 years. Cutaneous melanoma was the most common type. There was strong correlation between p16 and ki67 expression. P16 was seen in all cases. High ki67 was seen in 85% of cases. [ABSTRACT FROM AUTHOR]

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Cervical cancer is one of the most common malignant cancers in women worldwide. The 5-year survival rate is 65%; nevertheless, it depends on race, age, and clinical stage. In the oncogenesis of cervical cancer, persistent HPV infection plays a pivotal role. It disrupts the expression of key proteins as Ki-67, p16, involved in regulating the cell cycle. This study aimed to identify the potential role of testin in the diagnosis of cervical precancerous lesions (CIN). The study was performed on selected archival paraffin-embedded specimens of CIN1 (31), CIN2 (75), and CIN3 (123). Moderate positive correlation was observed between testin and Ki-67 as well as testin and p16 expression in all dysplastic lesions (r = 0.4209, r = 0.5681; p < 0.0001 for both). Statistical analysis showed stronger expression of the testin in dysplastic lesions vs. control group (p < 0.0001); moreover, expression was significantly higher in HSIL than LSIL group (p < 0.0024). In addition, a significantly stronger expression of testin was observed in CIN3 vs. CIN1 and CIN3 vs. CIN2. In our study, expression of Ki-67, p16, and testin increased gradually as the lesion progressed from LSIL to HSIL. The three markers complemented each other effectively, which may improve test sensitivity and specificity when used jointly.

Expression of Ki-67 and P16 proteins in cervical cancer and precancerous lesions of young women and the diagnostic value for cervical cancer and precancerous lesions were investigated. A total of 64 paraffin-embedded specimens of uterus tissue from young female patients who were admitted to Jiading District Central Hospital Affiliated to Shanghai University of Medicine and Health Sciences from January 2015 to December 2017 were selected. According to pathological examination, the specimens were divided into chronic cervicitis group (control group, 10 cases), low-grade squamous intraepithelial lesion (LSIL) group (12 cases), high-grade squamous intraepithelial lesion (HSIL) group (20 cases) and squamous carcinoma of the cervix (SCC) group (22 cases). Expression of Ki-67 and P16 protein was detected by immunohistochemistry and the diagnostic values were analyzed. Positive rates of Ki-67 and P16 expression in HSIL and SCC groups were significantly higher than those in LSIL and control groups (P<0.05), but there was no significant difference between LSIL and control groups (P>0.05). Spearman's analysis showed that the expression levels of Ki-67 and P16 were positively correlated with the degree of cervical lesions (rs=0.725; rs=0.829), and their expression levels were also positively correlated (rs=0.772). Sensitivity and specificity analysis showed that the Ki-67 diagnosis has higher sensitivity (95.2%), but the specificity is poor (86.7%). Diagnosis using P16 has high specificity (94.6%), but the sensitivity is poor (85.4%). When the two were combined for diagnosis, sensitivity (94.8%) and specificity (93.2%) were both at a high level. The combined detection of Ki-67 and P16 protein has a high application prospect as an auxiliary diagnosis of SCC. [ABSTRACT FROM AUTHOR]

Objective: To investigate the diagnostic value and prognostic value of HPV and P16 protein in patients with HSIL and to provide a reference for the clinical diagnosis and assessment of the prognosis of patients with HSIL. Methods: The surgical treatment of HSIL patients from January 2013 to January 2015 in our hospital were selected. All patients were routinely tested for HPV and P16 protein, All patients were followed up for 1 year. Patients were divided into progressive group and quiescent group according to whether the disease progressed one year after surgery. Preoperative HPV and P16 protein levels were compared between the two groups. Using receiver operating curve (ROC curve) Analysis of HPV diagnostic value of HSIL. The levels of HPV and P16 protein in the two groups were analyzed and compared. Results: The quantitative level of high-risk HPV-DNA after LEEP was significantly lower than that before operation. The level of P16 protein in preoperative patients was higher than that before operation, and the difference was statistically significant. There were 21 patients in the postoperative progression group, and the average HPV-DNA content in the patients in the progression group was higher than that in the control group within one year after operation. The difference was statistically significant. The P16 protein level in patients in advanced group was significantly higher than that in resting group. Preoperative HPV-DNA levels and P16 protein levels in patients with progressive disease were significantly higher than those in still group. ROC curve analysis showed that the cut-off value of 2.441, HPV-DNA prediction of HSIL patients one year after the recurrence of the sensitivity was 95.12%, the specificity was 76.16%, under the curve area of 0.878; 7.4 cut-off value, P16 The predictive value of HSIL patients recurrence after 1 year was 71.95%, specificity was 66.67%, and the area under the curve was 0.753. The recurrence group HPV-DNA content and P16 protein level showed a significant positive correlation, with statistical significance. Conclusions: LEEP can reduce the postoperative levels of HPV and P16 protein in patients with HSIL. The HPV and P16 protein levels are of high value for the early diagnosis of HSIL and the prediction of postoperative disease progression. [ABSTRACT FROM AUTHOR]

An eight-year-old gelding, Wielkopolski Horse was presented with a pink tumour, which filled the entire palpebral fissure of the left eye. Ultrasonography revealed it to be well-demarcated from the cornea mass, which covered its entire surface. Due to the extensive size of the lesion and the lack of owner's consent to post-operative treatment, it was decided to perform enucleation. A histopathological examination revealed corneal squamous cell carcinoma (CSCC). The primary cause of the tumour has not been established. Immunohistochemistry was negative for p16 immunoreactivity which is typical for the E7 oncoprotein in PV infection, and is suspected of involvement in the aetiopathogenesis of ocular squamous cell carcinoma (OSCC).

Background: Long-term smoking and drinking are known to contribute to the onset of tongue cancer (TC). However, the increasing incidence of TC in younger adults has been suggested to be associated with other factors. Objectives: The present study investigated the relationship between TC and human papillomavirus (HPV) infection. Material and methods: Clinical records and surgically resected specimens from 86 patients (<40-years-old, n = 12; ≥40-years-old, n = 74) with TC were analyzed. Strong nuclear and cytoplasmic p16 staining was considered positive. HPV DNA (high-risk subtypes: 16, 18, 31, 33, 35, 52b, and 58; low-risk subtypes: 6 and 11) was detected using consensus primer-mediated polymerase chain reaction. Results: Strong p16 expression was observed in 10 (11.6%) patients. HPV DNA was detected in 9 (10.5%) patients (high-risk subtypes, n = 2; low-risk subtypes, n = 7). Strong p16 expression was observed more frequently among younger adults than among older adults (33.3% vs. 8.1%; p = .045). p16 staining did not correlate with the detection of HPV DNA (correlation coefficient, 0.113; p = .300). Conclusions and significance: In TC, p16 expression was not associated with HPV infection, suggesting that it may be caused by a different mechanism. [ABSTRACT FROM AUTHOR]

Background: Long-term smoking and drinking are known to contribute to the onset of tongue cancer (TC). However, the increasing incidence of TC in younger adults has been suggested to be associated with other factors. Objectives: The present study investigated the relationship between TC and human papillomavirus (HPV) infection. Material and methods: Clinical records and surgically resected specimens from 86 patients (<40- years-old, n ¼ 12; 40-years-old, n ¼ 74) with TC were analyzed. Strong nuclear and cytoplasmic p16 staining was considered positive. HPV DNA (high-risk subtypes: 16, 18, 31, 33, 35, 52b, and 58; low-risk subtypes: 6 and 11) was detected using consensus primer-mediated polymerase chain reaction. Results: Strong p16 expression was observed in 10 (11.6%) patients. HPV DNA was detected in 9 (10.5%) patients (high-risk subtypes, n ¼ 2; low-risk subtypes, n ¼ 7). Strong p16 expression was observed more frequently among younger adults than among older adults (33.3% vs. 8.1%; p ¼ .045). p16 staining did not correlate with the detection of HPV DNA (correlation coefficient, 0.113; p ¼ .300). Conclusions and significance: In TC, p16 expression was not associated with HPV infection, suggesting that it may be caused by a different mechanism. [ABSTRACT FROM AUTHOR]

Objectives: Randomized trials evaluating cisplatin versus cetuximab chemoradiation (CRT) for p16+ oropharyngeal cancer (OPC) have yet to report preliminary data. Meanwhile, as a preemptive step toward morbidity reduction, the off-trial use of cetuximab in p16+ patients is increasing, even in those who could potentially tolerate cisplatin. The purpose of this study was to compare the efficacy of cisplatin versus cetuximab CRT in the treatment of p16+ OPC and to identify prognostic factors and predictors of tumor response.Materials and Methods: Cases of p16+ OPC treated with cisplatin or cetuximab CRT at our institution from 2010 to 2014 were identified. Recursive partitioning analysis (RPA) classification was used to determine low-risk (LR-RPA) and intermediate-risk (IR-RPA) groups. Log-rank/Kaplan-Meier and Cox Regression methods were used to compare groups.Results: We identified 205 patients who received cisplatin (n = 137) or cetuximab (n = 68) CRT in the definitive (n = 178) or postoperative (n = 27) setting. Median follow-up was 3 years. Cisplatin improved 3-year locoregional control (LRC) [92.7 vs 65.4%], distant metastasis-free survival (DMFS) [88.3 vs 71.2%], recurrence-free survival (RFS) [86.6 vs 50.6%], and overall survival (OS) [92.6 vs 72.2%] compared to cetuximab [all p < .001]. Concurrent cisplatin improved 3-year OS for LR-RPA (97.1 vs 80.3%, p < .001) and IR-RPA (97.1 vs 80.3%, p < .001) groupings.Conclusion: When treating p16+ OPC with CRT, the threshold for substitution of cisplatin with cetuximab should be maintained appropriately high in order to prolong survival times and optimize locoregional and distant tumor control. When cetuximab is used in cisplatin-ineligible patients, altered fractionation RT should be considered in an effort to improve LRC. [ABSTRACT FROM AUTHOR]

Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated with susceptibility to beta-human papilloma virus (HPV) infection. EV patients develop disseminated warts and non-melanoma skin cancer, mainly squamous cell carcinomas (SCC) that are locally aggressive. EV pathogenesis is not yet fully understood, but alterations in the p16 gene play a role in the pathogenesis of neoplasms caused by high-risk genital HPV. To explore its role in EV lesions, we compared p16 expression in SCC from patients with and without EV. Tissue microarray slides composed of 27 SCC from EV patients, and 35 from non-EV patients were stained with an anti-p16 antibody. Twenty (74%) EV tumors exhibited diffuse (nuclear and cytoplasmic) p16 expression, one (4%) displayed focal expression, and six (22%) displayed no p16 staining. Eleven (31%) SCC from non-EV patients presented diffuse p16 staining, 14 (40%) displayed focal expression and 10 (29%) did not express p16. The frequency of diffuse p16 expression was higher in EV tumors than in SCC from patients without EV. The frequency of diffuse p16 expression in moderately and poorly differentiated EV-SCC was similarly higher than non-EV tumors with the same degree of differentiation. The diffuse expression of p16 in EV-SCC suggests that changes in the p16 gene, probably resulting in a functionally defective protein, may be one factor determining the locally aggressive clinical behavior of SCC in young EV patients. [ABSTRACT FROM AUTHOR]

Objective Bmi-1, a putative proto-oncogene, is a core member of the polycomb gene family, which is expressed in many human tumors. The p16 protein negatively regulated cell proliferation, whereas CD44v6 is associated with proliferation as an important protein. Additionally, CD44v6 is an important nuclear antigen closely correlated to tumor metastasis. The present study aims to investigate the expression and significance of Bmi-1, p16, and CD44v6 in uterine cervical carcinoma (UCC).Methods A total of 62 UCC, 30 cervical neoplasic, and 20 normal cervical mucosal tissues were used in the current study. The expression of Bmi-1, p16, and CD44v6 in these tissues was determined using immunohistochemical assay. The relationships among the expression of these indices, the clinicopathologic features of UCC, and the survival rate of UCC patients were also discussed. The correlation between Bmi-1 protein expression and p16 or CD44v6 protein in UCC was analyzed.Results The expression of Bmi-1, p16, and CD44v6 was significantly high in cervical carcinoma compared with that in the cervical neoplasia and normal colorectal mucosa (PPP0.05). The Kaplan-Meier survival analysis showed that the over-expression of Bmi-1 significantly decreased the survival rate of UCC patients (Pr=0.419, P=0.001).Conclusions The over-expression of Bmi-1 and CD44v6 protein closely correlate to the tumorigenesis, metastasis, and prognosis of UCC. Bmi-1 and CD44v6 may be used to predict the prognosis of cervical carcinoma. Bmi-1 may indirectly regulate the expression of CD44v6 in UCC patients. The positive expression of p16 protein is possibly associated with the tumorigenesis, but not with the metastasis or prognosis of UCC.

Background and objective hTERT and p16 are involved in oncogenesis and development of tumor. The aim of this study is to investigate the expression of human telomerase reverse transcriptase (hTERT) and p16 in non-small cell lung cancer (NSCLC). Methods The quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and immunohistochemistry were applied to detect the hTERT and p16 in tissue of 21 cases of lung benign diseases and 117 of non-small cell lung cancer and adjacent tissues, respectively. Results hTERT mRNA levels from NSCLC in 117 patients and normal lung tissue in 21 normal controls were 2.937±0.836 and 2.042±0.378, respectively (t=-5.242, P < 0.01). Expression of p16 protein was observed in 85.7% of normal tissues, while 47.9% of lung cancer tissues showed p16 protein expression (P=0.004). The expression of hTERT mRNA was significantly correlated with the histology (P < 0.05); the expression of p16 protein was significantly correlated with the clinical stage, degree of differentiation and lymph node metastasis (P < 0.05). The significant correlation between the expression of hTERT and p16 (P < 0.05). Conclusion The hTERT may be useful in clinical diagnosis of NSCLC. Expression of hTERT and p16 is related to the carcinogenesis and development of NSCLC.

We examined CpG island methylation in p16 gene and its effect on p16 protein expression in tetralogy of Fallot (ToF) patients to explore its potential implications in the development and progression of ToF. The study subjects consisted of 75 healthy controls and 63 ToF patients recruited at Linyi People's Hospital between January 2012 and June 2014. The 4 mL of peripheral venous blood of each subject was obtained and saved in ethylene diamine tetraacetic acid (EDTA) tubes. Methylation-specific polymerase chain reaction (MSP) was employed to detect CpG island methylation in p16 promoter region and Western blotting was used to detect p16 expression of all subjects. Real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) was performed to test p16 mRNA expression. The results showed that p16-methylation rates in ToF group were significantly higher than the control group (ToF group, 58.73%; control group, 13.33%; P < 0.001). Remarkably, Western blotting and FQ-PCR results derived from RVOT revealed that p16 protein expression was significantly lower in ToF group compared to the control group (0.76 ± 0.21 versus 2.31 ± 0.35; P < 0.001), and p16 gene expression was also markedly decreased in ToF group (1.212 ± 0.152 versus 1.346 ± 0.191, P < 0.001). Additionally, our analysis suggested that CpG island methylation in p16 promoters in ToF patients was negatively correlated with p16 protein and gene expression (both P < 0.05). Our study reports that high CpG island methylation of p16 gene and loss of p16 protein expression associate with the development and progression of ToF, which may have significant therapeutic applications for ToF. [ABSTRACT FROM AUTHOR]

Background Expression of p16 is frequently evaluated in melanocytic lesions. Expression of p16 in cutaneous histiocytic, fibrohistiocytic and undifferentiated lesions has not been well characterized. Methods We evaluated p16 expression in a cohort of histiocytic (reticulohistiocytoma, Langerhans cell histiocytosis, xanthogranuloma, Rosai Dorfman disease and xanthoma), fibrohistiocytic (dermatofibroma, epithelioid fibrous histiocytoma and dermatofibrosarcoma protuberans) and undifferentiated (atypical fibroxanthoma and pleomorphic undifferentiated sarcoma) lesions. A group of melanocytic lesions (Spitz nevus, ordinary nevus, spitzoid melanoma and non-spitzoid melanoma) were also evaluated as reference. Each case was scored by the proportion of p16-positive cells and by staining intensity. Results Immunoreactivity for p16 was found in almost all histiocytic (28/30, 93%) and fibrohistiocytic (22/24, 92%) lesions. About half of the undifferentiated lesions also exhibited p16 staining (9/17, 53%). Most of the melanocytic cases examined in this study expressed p16. A wide range of staining intensity and proportion of p16-positive cells was observed in most groups. Conclusion Expression of p16 is common, albeit variable in proportion and intensity, amongst a wide variety of cutaneous histiocytic, fibrohistiocytic and undifferentiated lesions. Further studies are required to determine if p16 expression is useful in distinguishing benign from malignant neoplasms of these types. [ABSTRACT FROM AUTHOR]

Objective: Human papillomavirus (HPV) is a causal and prognostic factor for oropharyngeal cancer, but its role in squamous cell carcinoma of the oral cavity (SCCOC) is unclear. We sought to clarify HPV's role in SCCOC.Materials and Methods: Patients with newly diagnosed SCCOC (N=460) were prospectively recruited, treated, and followed at one institution. p16/HPV status was determined by p16 immunohistochemistry (IHC) (N=210), PCR-based HPV 16/18 E6/7 DNA testing (N=403), and/or HPV in situ hybridization (ISH) (N=178). Kaplan-Meier curves and log-rank tests were used to compare survival by p16/HPV status.Results: p16 expression was detected in 30% of tumors (62/210) and HPV 16/18 E6/7 DNA in 28% (114/403), although correlation between these two assays was poor (r=-0.01). Patients with p16-positive tumors were more likely to be younger and have primary tumors of the oral tongue. Only 4% of tumors (7/171) were positive for HPV by ISH. Comparisons of patients with p16-positive and p16-negative tumors, patients with HPV-positive and HPV-negative tumors by PCR, and patients with HPV-positive and HPV-negative tumors by ISH showed no significant differences in disease-specific or disease-free survival by p16/HPV status. When we applied a more stringent definition of HPV positivity based on a combination of assay results, only 10 of 166 tumors were HPV positive, and there were no significant differences in demographic, exposure, clinical, or survival characteristics between these patients and the 156 HPV-negative patients.Conclusions: Very few patients with SCCOC have HPV-driven tumors. SCCOC that overexpresses p16 may be a unique subset deserving of further study. [ABSTRACT FROM AUTHOR]

The purpose of this study was to accomplish a comparative assessment between the immune histochemical and the immunocytochemical expression of p16 protein and L1 major capsid protein of HPV respectively, in cervical squamous intraepithelial lesions with low and high grade, in order to determine, through morphological and clinical correlations, their applicability into practice when diagnosing and further monitoring the patients. There were 119 patients included in the study, having a mean age of 40, cytologically and histopathologically diagnosed in the Laboratory of Pathologic Anatomy of "Elena Doamna" Third Clinic of Obstetrics and Gynaecology in Iaşi. 42 of these patients were diagnosed with LSIL (low grade squamous intraepithelial lesion) and 51 with HSIL (high grade squamous intraepithelial lesion). The cervical-vaginal smears were interpreted using the Papanicolaou method. The conventional smears were assessed for the immunoexpression of L1 capsid protein HPV, and the corresponding biopsies for p16 immunoexpression. The colouring pattern of p16 protein was predominantly nuclear, with an occasional cytoplasmic positivity. P16 biomarker was positive in cytological smear prepared in a liquid environment for 71.6% of the patients, without significant differences for those over 40 years old (69.6% vs 69.0%; p=0.887), with an increase in positivity from 54.8% in LSIL to 98% in HSIL (p=0.05); the oncogenic risk was 1,55 higher (RR=1.55; IC95%: 1.19÷2.01). L1 protein was detected in 34,5% of the patients, the expression tending to increase in parallel with the increase in the severity of the lesions (66.7% LSIL; 17.6% HSIL). The presence of L1 protein in the patients with an increased risk of malignant transformation of HPV seems to be a protective factor (RR=0.42; IC95%: 0.27÷0.66). The immunoexpression of L1 HPV protein has clinical applications in assessing the progression of cervical pre-cancer lesions. The analysis of p16 status, in parallel with the expression of L1 HPV protein, can be very useful in assessing the risk of progression for cervical intraepithelial squamous lesions. The preventive conduct supported by a primary care screening, leads to a decrease in the morbidity by pre-invasive lesions and an evolution with a favourable prognostic. [ABSTRACT FROM AUTHOR]

Aim Our recent work suggested that circulating IgG antibodies to a linear peptide derived from p16 protein were significantly increased in patients with lung cancer. The present study was then designed to test whether such autoantibodies were also altered in esophageal cancer. Methods An enzyme-linked immunosorbent assay was developed in-house to determine circulating IgA and IgG antibodies against p16 protein-derived antigens in 97 patients with esophageal squamous cell carcinoma ( ESCC) and 226 healthy subjects. Results The levels of anti-p16 IgG but not IgA antibodies were significantly higher in the patient group than the control group ( t = 2.81, P = 0.0052); circulating anti-p16 IgG levels were inversely correlated with stages of ESCC ( r = −0.30, df = 81, P = 0.0058) and patients with stage I of ESCC had the highest IgG level among all four stages ( t = 5.25, P ≤ 0.0001, compared with control subjects). There was no correlation between the levels of IgA and IgG either in the patient group ( r = −0.05, df = 86, P = 0.627) or in the control group ( r = −0.1, df = 205, P = 0.146). Conclusion Circulating IgG autoantibody to p16 protein may be a potential biomarker for early diagnosis of esophageal cancer. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate prevalence of high-risk human papillomavirus (HR-HPV) infection in sinonasal carcinomas by immunohistochemistry, in situ hybridization, and polymerase chain reaction, detecting p16(INK4a) protein (p16) expression and presence of both HPV DNA and HPV E6/E7 messenger RNA (mRNA). The study comprised 47 males and 26 females, aged 23-83 years (median 62 years), mostly (67 %) with a squamous cell carcinoma (SCC). Of the tumors, 53 % arose in the nasal cavity, 42 % in the maxillary sinus, and 5 % in the ethmoid complex. The follow-up period ranged 1-241 months (median 19 months). HPV16, HPV18, or HPV35 were detected in 18/73 (25 %) tumors, 17 SCCs, and 1 small cell neuroendocrine carcinoma. There was a strong correlation between results of HPV detection methods and p16 expression (p < 0.005). HPV-positive SCCs occurred more frequently in smokers (p = 0.04) and were more frequently p16-positive (p < 0.0001) and nonkeratinizing (p = 0.02), the latter occurring more commonly in nasal cavity (p = 0.025). Median survival for HPV-positive SCC patients was 30 months, while for HPV-negative SCC patients was 14 months (p = 0.23). In summary, we confirm that HR-HPV is actively involved in the etiopathogenesis of a significant subset of sinonasal SCCs. p16 may be used as a reliable surrogate marker for determination of HPV status also in sinonasal SCCs. Although we observed a trend toward better overall survival in HPV-positive SCCs, the prognostic impact of HPV status in sinonasal carcinomas needs to be elucidated by further studies. [ABSTRACT FROM AUTHOR]

An eight-year-old gelding, Wielkopolski Horse was presented with a pink tumour, which filled the entire palpebral fissure of the left eye. Ultrasonography revealed it to be well-demarcated from the cornea mass, which covered its entire surface. Due to the extensive size of the lesion and the lack of owner's consent to postoperative treatment, it was decided to perform enucleation. A histopathological examination revealed corneal squamous cell carcinoma (CSCC). The primary cause of the tumour has not been established. Immunohistochemistry was negative for p16 immunoreactivity which is typical for the E7 oncoprotein in PV infection, and is suspected of involvement in the aetiopathogenesis of ocular squamous cell carcinoma (OSCC). [ABSTRACT FROM AUTHOR]

Overexpression of the p16 protein has been reported in breast cancer and may trigger the secretion of antibodies against itself. Circulating anti-p16 antibodies that were detected with a recombinant protein have been reported in breast cancer. The present study was designed to determine whether the levels of circulating IgG antibody to p16 protein-derived linear antigens are altered in breast cancer. An enzyme-linked immunosorbent assay (ELISA) was developed in-house to determine circulating IgG against peptide antigens derived from the p16 protein in 152 female breast cancer patients and 160 healthy female subjects. The Student's t-test revealed that breast cancer patients exhibited significantly higher levels of anti-p16 IgG antibody compared to control subjects (t=2.02, P=0.045). In addition, ductal cancer appeared to be the main type contributing to the increased levels of circulating anti-p16 antibodies (t=2.08, P=0.038). Of all four stages of breast cancer, stage I was associated with the highest levels of IgG antibody (t=2.02, P=0.045) and receiver operating characteristic (ROC) analysis demonstrated that the area under the ROC curve was 0.74 (95% confidence interval: 0.65-083) and that the sensitivity against a specificity of 90% was 30.3%. Therefore, the levels of circulating IgG antibody to the p16 protein may be a potential biomarker for early diagnosis of breast cancer. [ABSTRACT FROM AUTHOR]

Summary Objectives The clinical behavior of oral tongue squamous cell carcinoma (OTSCC) can be unpredictable, and even small tumors may behave aggressively. Toll-like receptors (TLRs) are pattern-recognition molecules involved in innate immunity, and they are also expressed in many types of cancer. TLRs play an apparently pivotal role in some cancers related to tumor progression and, conversely, cancer inhibition, however their role in oral cancer is unclear. We therefore studied the expression of TLR-2, -4, -5, -7, and -9 in early-stage OTSCC. Materials and methods Tissue microarray technique and immunohistochemistry was employed to define the expression of TLRs from the tumors of 73 consecutive patients with Stage I-II OTSCC. Immunoexpression scores were compared with patient and tumor related characteristics and survival. Results All TLRs were expressed in OTSCC tissue. High/strong TLR-2, -4, and -9 expression correlated with deeper tumor invasion. Cytoplasmic TLR-2 and -4 also correlated significantly with higher tumor grade, whereas high TLR-5 expression associated with lower tumor grade. High expression of TLR-9 correlated with advanced tumor size. Negative or mild TLR-5 expression predicted poor disease-specific survival. Conclusion All the studied TLRs showed high expression in early-stage OTSCC. More importantly, TLR-2, -4, and -9 seemed to predict invasive tumor growth. [ABSTRACT FROM AUTHOR]

Studies have shown fibers to be effective in reducing the appearance of aberrant crypt foci (ACF) in rodents. Objective: The goal of this study was to investigate the preventive effects of fructooligosaccharide (FOS) and inulin prebiotics on the appearance of ACF in mice. Materials and Methods: The techniques used were: RT-PCR to evaluate the gene expression of pl6, p21, p54, cyclin D1 and cyclin E in the distal colon; the quantification of Number of aberrant crypt foci (ACF) and measurement of catalase activity in the liver and distal colon. The animals were divided into five treatments (n=8); C-: AIN93M diet without fibers + DMH (1,2-dimethylhydrazine); INL: AIN93M diet with inulin; INLCA: AIN93M diet with inulin + DMH; FOS: AIN93M diet with FOS; FOSCA: AIN93M diet with FOS + DMH, during 15 weeks. Results: Inulin prevented the appearance of ACF in the proximal, middle and distal colon, compared to the control without fibers. In the middle and distal colon, FOS was also effective in preventing the incidence of ACF. This effectiveness may be attributed to the increased gene expression of pl6 following FOS treatment. Both prebiotics also decreased catalase activity in the distal colon, thus suggesting an antioxidant effect. Conclusion: These results suggesting an antioxidant effect prebiotics that may be attributed to the increased gene expression of p 16. [ABSTRACT FROM AUTHOR]

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Association between verrucous carcinoma ( VC) of the head and neck and human papillomaviruses ( HPV) is highly controversial. Previous prevalence studies focused mostly on α- PV, while little is known about other PV genera. Our aim was to investigate the prevalence of a broad spectrum of HPV in VC of the head and neck using sensitive and specific molecular assays. Formalin-fixed, paraffin-embedded samples of 30 VC and 30 location-matched normal tissue samples were analysed, by using six different polymerase chain reaction-based methods targeting DNA of at least 87 HPV types from α- PV, β- PV, γ- PV and μ- PV genera, and immunohistochemistry against p16 protein. α- PV, γ- PV and μ- PV were not detected. β- PV DNA was detected in 5/30 VC (16.7%) and in 18/30 normal tissue samples (60.0%): HPV-19, -24 and -36 were identified in VC, and HPV-5, -9, -12, -23, -24, -38, -47, -49 and -96 in normal tissue, whereas HPV type was not determined in 2/5 cases of VC and in 6/18 normal tissue samples. p16 expression was detected in a subset of samples and was higher in VC than in normal tissue. However, the reaction was predominantly cytoplasmic and only occasionally nuclear, and the extent of staining did not exceed 75%. Our results indicate that α- PV, γ- PV and μ- PV are not associated with aetiopathogenesis of VC of the head and neck. β- PV DNA in a subset of VC and normal tissue might reflect incidental colonization, but its potential biological significance needs further investigation. [ABSTRACT FROM AUTHOR]

Overexpression of tumor-associated antigens (TAAs) has been reported in many types of cancer and may trigger secretion of their autoantibodies. The present work was thus designed to test whether circulating antibody to p16 protein-derived antigens was altered in lung cancer. Two hundred seventy-one patients with non-small cell lung cancer (NSCLC) and 226 control subjects matched in age, gender, and smoking history were recruited in this study. The levels of circulating anti-p16 IgA and IgG antibodies were tested using an enzyme-linked immunosorbent assay (ELISA) developed in-house with linear peptide antigens derived from p16 protein. Student's t test showed that patients with NSCLC had a significant higher level of anti-p16 IgG antibody than control subjects ( t = 2.74, P = 0.0063) but did not have a significant increase in IgA antibody levels ( t = 1.92, P = 0.056). The sensitivity against >90 % specificity was 19.7 % for the IgG assay with an inter-assay deviation of 11.6 %, and 10.3 % for the IgA assay with an inter-assay deviation of 14.7 %. Based on a cut-off value determined by the 99th percentile of control IgG levels, the anti-p16 IgG positivity was 6.7 % in patients with NSCLC compared to 0.88 % in control subjects ( χ = 10.58, P = 0.001, OR = 7.97, 95 % CI 1.84-34.85). Circulating anti-p16 IgG levels were increased with stages of NSCLC, and patients with stage IV NSCLC had the highest IgG level among all four stages ( t = 2.42, P = 0.016, compared with the control group). Pearson correlation analysis showed a significant correlation between circulating levels of IgA and IgG in the patient group ( r = −0.2, df = 236, P = 0.0021) but not in the control group ( r = −0.1, df = 205, P = 0.146). Circulating IgG antibody to p16 protein may be a potential biomarker with prognostic values for lung cancer. [ABSTRACT FROM AUTHOR]

Desmoplastic melanoma can be difficult to distinguish from desmoplastic melanocytic nevi both clinically and histopathologically. Several attempts have been made to explore the use of ancillary studies to facilitate this distinction. Prior work has suggested that immunohistochemical expression of p16 could help distinguish sclerosing Spitz nevi from desmoplastic melanomas. We re-evaluated the expression of p16 in 22 desmoplastic melanomas (13 mixed and 9 pure desmoplastic tumors) and five desmoplastic melanocytic nevi (three desmoplastic Spitz nevi and two congenital melanocytic nevi with prominent dermal sclerosis). All desmoplastic melanocytic nevi were strongly immunoreactive for p16. Of the 22 desmoplastic melanomas, 6 tumors failed to label for p16, 10 were focally positive, but 6 tumors were diffusely immunoreactive. The latter finding is relevant, as it points to limitations in the diagnostic value of immunohistochemical staining for p16 for the diagnosis of desmoplastic melanocytic proliferations. Diffuse staining for p16 is not restricted to desmoplastic Spitz nevi but can also occur in a subset of desmoplastic melanomas, and this warrants caution in the use of this marker for diagnostic purposes. [ABSTRACT FROM AUTHOR]