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Background: The DNA ploidy and the S phase fraction (SPF) are associated with advanced tumors progression. The present study aimed to investigate the clinicopathological behavior of oral squamous cell carcinoma(OSCC) and the prognostication of the DNA ploidy and the SPF on its clinical outcomes. Methods: This a prospective longitudinal study of 93 OSCC patients (186 specimens). Using high resolution flowcytometry, DNA analysis and SPF were performed for the primary tumor, field of cancerization and a control normal field. The patients were followed clinically for the development of recurrence or second primary tumor(SPT). Results: All the 93 patients are associated with wide field of cancerization. Out of the total number of cases, 28 (30%) patients developed recurrence. Of them 17 (18.3%) had regional recurrence, and eight (8.6%) had local recurrence. Second primary tumors were identified in 14 (15.1%) of the cases. Nodal metastasis, overall recurrence and SPTs were significantly associated with DNA aneuploidy and high SPF. High SPF and DNA hyperploidy showed a 28% increased risk of local recurrence (P.value = 0.032). Conclusion: In a series of 93 oral cancers who had wide field of cancerization, 30% of the patients developed recurrence, and 15% developed second primary tumors. The DNA ploidy and the SPF were independent prognosticators for the prediction of OSCC outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background The DNA ploidy and the S phase fraction (SPF) are associated with advanced tumors progression. The present study aimed to investigate the clinicopathological behavior of oral squamous cell carcinoma(OSCC) and the prognostication of the DNA ploidy and the SPF on its clinical outcomes. Methods This a prospective longitudinal study of 93 OSCC patients (186 specimens). Using high resolution flowcytometry, DNA analysis and SPF were performed for the primary tumor, field of cancerization and a control normal field. The patients were followed clinically for the development of recurrence or second primary tumor(SPT). Results All the 93 patients are associated with wide field of cancerization. Out of the total number of cases, 28 (30%) patients developed recurrence. Of them 17 (18.3%) had regional recurrence, and eight (8.6%) had local recurrence. Second primary tumors were identified in 14 (15.1%) of the cases. Nodal metastasis, overall recurrence and SPTs were significantly associated with DNA aneuploidy and high SPF. High SPF and DNA hyperploidy showed a 28% increased risk of local recurrence (P.value = 0.032). Conclusion In a series of 93 oral cancers who had wide field of cancerization, 30% of the patients developed recurrence, and 15% developed second primary tumors. The DNA ploidy and the SPF were independent prognosticators for the prediction of OSCC outcomes.

Introduction: DNA ploidy (P), stroma fraction (S), and nucleotyping (N) collectively known as PSN, have proven prognostic accuracy in stage II colorectal cancer (CRC). However, few studies have reported on the prognostic value of the PSN panel in stage III colon cancer patients receiving capecitabine and oxaliplatin adjuvant chemotherapy. Objectives: This study aimed to validate PSN's prognostic impact on stage III colon cancer, identifying candidates for optimized adjuvant chemotherapy duration. Design: A retrospective analysis was conducted on a cohort of stage III colon cancer patients from April 2008 to June 2020. Methods: Postoperative pathological samples from stage III colon cancer patients who underwent radical surgery and postoperative adjuvant chemotherapy at Sun Yat-sen University Cancer Center were retrospectively collected. Automated digital imaging assessed PSN, categorizing risk groups. Kaplan–Meier, Cox regression, and time-dependent receiver operating characteristic analysis compared model validity. Results: Significant differences in 5-year disease-free survival (DFS) and overall survival (OS) were noted among PSN-based low-, moderate-, and high-risk groups (DFS: 92.10% versus 83.62% versus 79.80%, p = 0.029; OS: 96.69% versus 93.99% versus 90.12%, p = 0.016). PSN emerged as an independent prognostic factor for DFS [hazard ratio (HR) = 1.409, 95% confidence interval (CI): 1.002–1.981, p = 0.049] and OS (HR = 1.720, 95% CI: 1.127–2.624, p = 0.012). The PSN model, incorporating perineural invasion and tumor location, displayed superior area under the curve for 5-year (0.692 versus 0.553, p = 0.020) and 10-year (0.694 versus 0.532, p = 0.006) DFS than TNM stage. In the PSN high-risk group, completing eight cycles of adjuvant chemotherapy significantly improved 5-year DFS and OS compared to four to seven cycles (DFS: 89.43% versus 71.52%, p = 0.026; OS: 96.77% versus 85.46%, p = 0.007). Conclusion: The PSN panel effectively stratifies stage III colon cancer, aiding in optimized adjuvant chemotherapy duration determination. [ABSTRACT FROM AUTHOR]

Purpose: Post prostatectomy PSA kinetics and General Grade Groups (GGG) are the strongest prognostic markers of biochemical recurrence (BCR) and prostate cancer (PCa)-specific mortality after radical prostatectomy. Despite having low-risk PCa, some patients will experience BCR, for some, clinically significant BCR. There is a need for an objective prognostic marker at the time of prostatectomy to improve risk stratification within this population. In this study, we investigated the prognostic potential of DNA ploidy. Materials and Methods: Prostatectomy samples from 97 patients with GGG1 and GGG2 with a low-risk CAPRA-S score were included in this study. PCa tissue with the worst Gleason pattern underwent tissue disaggregation, cell isolation and staining with a DNA stoichiometric stain. Using image cytometry, DNA ploidy was measured and a Ploidy Score (PS) was generated. Results: Among the 97 patients, 79 had no BCR, 18 experienced BCR, of which 14 had a PSA doubling time (PSA-DT) >1 year (low-risk group) and 4 had a PSA-DT of <1 year (high-risk group). Using Logistic regression analysis, only pathological T stage (pT) and PS independently predicted BCR with PS being the most significant (p = 0.001). The number of aneuploid cells was significantly higher in the high-risk group compared to the other groups (p = 1.7x10-11). PS combined with GGG diagnosis further stratified risk groups of biochemical recurrence free survival within CAPRA-S low-risk cohort. Conclusion: DNA ploidy is an independent prognostic marker of BCR in low-risk PCa after radical prostatectomy, which could early on identify potentially aggressive PCa recurrences and introduce a more personalized approach to salvage treatments. [ABSTRACT FROM AUTHOR]

Background: This prospective observational study investigated the determinants of malignant transformation (MT) in localized oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL). Methods: Demographic, clinical, histological, and DNA ploidy status data were collected at enrolment. Survival analysis was performed (MT being the event of interest). Results: One‐hundred and thirty‐three patients with OL and 20 patients with PVL entered the study over 6 years (mean follow‐up 7.8 years). The presence of OED, DNA ploidy, clinical presentation, and lesion site were associated with MT in patients with OL in a univariate analysis. In a multivariate model, OED was the strongest predictor of MT in patients with OL. Adding DNA ploidy increased the model's predictive power. None of the assessed predictors was associated with MT in patients with PVL. Conclusions: DNA ploidy might identify a subset OL with low risk or minimal risk of MT, but it does not seem to be a reliable predictor in patients with PVL. [ABSTRACT FROM AUTHOR]

Malignant and potentially malignant epithelial lesions are often associated with various abnormalities such as epithelial dysplasia, abnormal DNA content, loss of heterozygosity, and chromosomal number aberrations. Screening and early detection of such abnormalities facilitates proper care and also helps to prevent further progression of potentially malignant lesions to malignancy. In such way, the presence of DNA aneuploidy in oral potentially malignant disorders (OPMDs) may serve as an indicator for the malignant transforming potential. Various assessment methods have been proposed to find the DNA ploidy status of cells. This current systematic review is mainly designed to assess the importance of ploidy status in OPMD while measuring the feasibility of using this biomarker for evaluating the hazard of malignant transformation. As an upshot of this systematic review, we can conclude that use of DNA ploidy status can serve as an independent bio-marker for predicting the malignant transformation of lesions. Furthermore, as a future scope the use of DNA ploidy analysis in normal mucosa of smokers will help to assess the malignancy risk and this technique might also help to predict the genetic predisposition of patients with malignancy. [ABSTRACT FROM AUTHOR]

Malignant and potentially malignant epithelial lesions are often associated with various abnormalities such as epithelial dysplasia, abnormal DNA content, loss of heterozygosity, and chromosomal number aberrations. Screening and early detection of such abnormalities facilitates proper care and also helps to prevent further progression of potentially malignant lesions to malignancy. In such way, the presence of DNA aneuploidy in oral potentially malignant disorders (OPMDs) may serve as an indicator for the malignant transforming potential. Various assessment methods have been proposed to find the DNA ploidy status of cells. This current systematic review is mainly designed to assess the importance of ploidy status in OPMD while measuring the feasibility of using this biomarker for evaluating the hazard of malignant transformation. As an upshot of this systematic review, we can conclude that use of DNA ploidy status can serve as an independent bio-marker for predicting the malignant transformation of lesions. Furthermore, as a future scope the use of DNA ploidy analysis in normal mucosa of smokers will help to assess the malignancy risk and this technique might also help to predict the genetic predisposition of patients with malignancy.

Simple Summary: In this work, we evaluated the prognostic value of the chromatin structure in patients with early-stage lung cancer. We assessed the associations of DNA ploidy, nucleotyping, and tumor–stroma ratio (TSR) with 5-year disease-free survival rates. Clarifying whether patients with homogeneous and heterogeneous chromatin can benefit from adjuvant chemotherapy can guide the decision-making regarding chemotherapy after lung cancer resection, improve the survival rate of patients, and reduce the incidence and cost of adverse events related to lung treatment. (1) Background: Chromatin structure typing has been used for prognostic risk stratification among cancer survivors. This study aimed to ascertain the prognostic values of ploidy, nucleotyping, and tumor–stroma ratio (TSR) in predicting disease progression for patients with early-stage non-small cell lung cancer (NSCLC), and to explore whether patients with different nucleotyping profiles can benefit from adjuvant chemotherapy. (2) Methods: DNA ploidy, nucleotyping, and TSR were measured by chromatin structure typing analysis (Matrix Analyser, Room4, Kent, UK). Cox proportional hazard regression models were used to assess the relationships of DNA ploidy, nucleotyping, and TSR with a 5-year disease-free survival (DFS). (3) Results: among 154 early-stage NSCLC patients, 102 were non-diploid, 40 had chromatin heterogeneity, and 126 had a low stroma fraction, respectively. Univariable analysis suggested that non-diploidy was associated with a significantly lower 5-year DFS rate. After combining DNA ploidy and nucleotyping for risk stratification and adjusting for potential confounders, the DNA ploidy and nucleotyping (PN) high-risk group and PN medium-risk group had a 4- (95% CI: 1.497–8.754) and 3-fold (95% CI: 1.196–6.380) increase in the risk of disease progression or mortality within 5 years of follow-up, respectively, compared to the PN low-risk group. In PN high-risk patients, adjuvant therapy was associated with a significantly improved 5-year DFS (HR = 0.214, 95% CI: 0.048–0.957, p = 0.027). (4) Conclusions: the non-diploid DNA status and the combination of ploidy and nucleotyping can be useful prognostic indicators to predict long-term outcomes in early-stage NSCLC patients. Additionally, NSCLC patients with non-diploidy and chromatin homogenous status may benefit from adjuvant therapy. [ABSTRACT FROM AUTHOR]

Objective To investigate the application value of liquid-based cytology, DNA ploidy and fluorescence in situ hybridization (FISH) in the diagnosis of upper tract urothelial carcinoma (UTUC). Methods From January 2013 to June 2021, 246 cases with suspected UTUC on CT or MRI images in the Army Medical Center of PLA were recruited and retrospectively analyzed. Among them, 190 cases were pathologically diagnosed as UTUC, 43 cases non-tumor lesions, and 13 cases other types of tumors. All the 246 cases were examined with liquid-based cytology of voided urine, 178 cases were also with DNA ploidy analysis and 167 cases with FISH. The diagnostic accuracy of liquid-based cytology, DNA ploidy and FISH alone or in combination was calculated and compared. Results The sensitivities of liquid-based cytology, DNA ploidy and FISH in the diagnosis of UTUC were 44.7%, 82.2%, and 57.9%, respectively; the specificities were 97.7%, 82.4%, and 92.3%, respectively. The diagnostic sensitivities of the above 3 methods for high-grade UTUC were 48.1%, 87.7%, and 60.7%, respectively, and for low-grade UTUC 25.0%, 52.4%, and 37.5%, respectively. When any one of the 3 methods is positive, the diagnostic sensitivity was increased to 93.8% (compared with the 3 methods being used alone, all P < 0.05). When any 2 of them were positive at the same time as the criteria for diagnosing UTUC (both negative or only 1 positive was regarded as negative), the positive predictive value and specificity of this combined diagnostic method were both 100%. Conclusion Urinary liquid-based cytology, DNA ploidy and FISH all are clinically valuable in the diagnosis of UTUC. The combination of the 3 methods can effectively improve the sensitivity or specificity of diagnosis, thereby helping to reduce the risk of missed diagnosis or misdiagnosis.

Abstract Background About 7 million people die from various types of cancer every year representing nearly 12.5% of deaths worldwide. This fact raises the demand to develop new, effective anticancer, onco-suppressive, and chemoprotective agents for the future fighting of cancers. Genistein exhibits pleiotropic functions in cancer, metabolism, and inflammation. It functions as an antineoplastic agent through its effect on the cell cycle, apoptotic processes, angiogenesis, invasion, and metastasis. Aim of the study The current study aimed to study the genistein onco-suppressive effects during 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters’ buccal pouch utilizing flow cytometry analysis (FMA), as a fast-diagnosing tool, in addition to the histopathology. Material and methods The buccal mucosa of adult male Syrian hamsters was painted with paraffin oil only (group 1), DMBA mixed in mineral oil (group 2), or orally administrated genistein along with painting DMBA (group 2B). The buccal mucosa was utilized for flow cytometric analysis and histopathological examination. Results Grossly, DMBA-induced carcinogenesis started at the 9th week. Progressive signs appeared in the following weeks reaching to large ulcerative oral masses and exophytic nodules at the 21st week. Histologically, invasive well-differentiated oral squamous cell carcinoma (OSCC) appeared in the underlying tissues from the 12th week, showing malignant criteria. Genistein had delayed clinicopathological change, which started 6 weeks later, than the DMBA-painted hamsters, as mild epithelial dysplastic changes. This became moderate during the last 6 weeks, without dysplastic changes. Flow cytometry revealed that DMBA led to considerable variation in DNA proliferation activity, aneuploid DNA pattern, in 47.22% of hamsters and significantly raised the S-phase fragment (SPF) values, which drastically reduced after genistein treatment. Conclusion Taken together, genistein could be employed as an onco-suppressive agent for carcinogenesis. Moreover, FMA could be used as an aiding fast tool for diagnosis of cancer.

Background: For clinically low-risk stage III colorectal cancer, the decision on cycles of adjuvant chemotherapy after surgery is disputed. The present study investigates the use of additional biomarkers of ploidy and stroma-ratio(PS) to stratify patients with low-risk stage III colorectal cancer, providing a basis for individualized treatment in the future. Methods: This study retrospectively enrolled 198 patients with clinical-low-risk stage III colorectal cancer (T1-3N1M0) and analyzed the DNA ploidy and stroma ratio of FFPE tumor tissues. The patients were divided into PS-low-risk group (Diploidy or Low-stroma) and PS-high-risk group (Non-diploid and High-stroma). For survival analyses, Kaplan–Meier and Cox regression models were used. Results: The results showed that the 5-year DFS of the PS-high-risk group was significantly lower than that in the PS-low-risk group (78.6 vs. 91.2%, HR = 2.606 [95% CI: 1.011–6.717], P = 0.039). Besides, in the PS-low-risk group, the 5 year OS (98.2 vs. 86.7%, P = 0.022; HR = 5.762 [95% CI: 1.281–25.920]) and DFS (95.6, vs 79.9%, P = 0.019; HR = 3.7 [95% CI: 1.24–11.04]) of patients received adjuvant chemotherapy for > 3 months were significantly higher than those received adjuvant chemotherapy for < 3 months. We also found that the PS could stratify the prognosis of patients with dMMR tumors. The 5-year OS (96.3 vs 71.4%, P = 0.037) and DFS (92.6 vs 57.1%, P = 0.015) were higher in the PS-low-risk dMMR patients than those in the PS-high-risk dMMR patients. Conclusion: In this study, we found that PS can predict the prognosis of patients with stage III low-risk CRC. Besides, it may guide the decision on postoperative adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract Background Colorectal cancer liver metastases (CRLM) has not been identified as a unified disease entity due to the differences in the severity of metastatic disease and tumor aggressiveness. A screen for specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of DNA ploidy, stroma fraction and nucleotyping of initially resectable liver metastases from patients with CRLM. Methods One hundred thirty-nine consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. DNA ploidy, stroma fraction and nucleotyping of liver metastases were evaluated using automated digital imaging systems. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox regression models. Results DNA ploidy was identified as an independent prognostic factor for RFS (HR, 2.082; 95% CI 1.053–4.115; P = 0.035) in the multivariate analysis, while stroma-tumor fraction and nucleotyping were not significant prognostic factors. A significant difference in 3-year RFS was observed among the low-, moderate- and high-risk groups stratified by a novel parameter combined with the tumor burden score (TBS) and DNA ploidy (72.5% vs. 63.2% vs. 37.3%, P = 0.007). The high-risk group who received adjuvant chemotherapy had a significantly better 3-year RFS rate than those without adjuvant chemotherapy (46.7% vs. 24.8%; P = 0.034). Conclusions Our study showed that DNA ploidy of liver metastases is an independent prognostic factor for patients with initially resectable CRLM after liver resection. The combination of DNA ploidy and TBS may help to stratify patients into different recurrence risk groups and may guide postoperative treatment among the patients.

Background: FxCycleTM Violet (FCV) based flow cytometric (FCM) DNA ploidy analysis is a rapid and simple tool that can substantiate in characterizing the biological behaviour across the spectrum of haematological malignancies and correlates with cytogenetic studies. Materials and Methods: In this prospective study, we performed simultaneous immunophenotyping with FCV based on ploidy analysis in n=132 consecutive new samples, comprising n=110 samples of haemato-lymphoid neoplasms, including acute leukemias (n=67, 60.9%), CML with myeloid blast crisis (n=1, 0.9%), MDS with excess blasts (n=2, 1.8%), mature B cell/ T cell neoplasms (n=37, 33.7%), multiple myeloma (n=3, 2.7%) along with n=22 normal samples. The FCM DNA data was compared with corresponding conventional karyotyping results, wherever available. Results: In FCM ploidy analysis (n=110), the overall DNA index (DI) ranged from 0.81 to 2.17 and S-Phase fraction (SPF) from 0.1-31.6%. Diploidy was seen in n = 90 (81.8%), low-hyperdiploidy in n = 10 (9.1%), highhyperdiploidy in n = 7 (6.4%) with one case each (0.9% each) having near-tetraploidy, high-hypodiploidy and low-hypodiploidy. The DI of all viable cell populations in normal samples ranged from 0.96-1.05. Conventional karyotyping was performed in n=76/110 cases (70%) with n= 11/76 (15%) culture failures. The modal chromosome number ranged from 45 to 63. A concordance of 95.4% (n=62/65) was noted with corresponding FCM DI. Conclusion: FCV-based ploidy is a sensitive technique that provides complementary information and ascertains a strong correlation with conventional cytogenetics across all haemato-lymphoid neoplasms. It can detect aneuploidy in all B-ALL and myeloma cases, even in hemodiluted samples with cytogenetic culture failure; supplement the diagnoses of erythroleukemia, and provide a useful screen for a higher grade lymph node disease in lymphoma cases with SPF > 3%. [ABSTRACT FROM AUTHOR]

Background: Methods to analyze progression of carcinogenesis and stage of cancer are vital nowadays due to the high prevalence of these lesions. DNA ploidy analysis is one such important method in early diagnosis and improving prognosis. Aims and Objectives: The aim of this study was to correlate histopathological grading and DNA ploidy in oral leukoplakia, oral submucous fibrosis (OSMF), and oral squamous cell carcinoma (OSCC) cases. Materials and Methods: Our study included 80 subjects, grouped into 4 groups of 20 each of OSCC, leukoplakia, OSMF, and healthy individuals. Histopathological grading was carried out in study cases, DNA ploidy was estimated using flow cytometry, and both the findings were correlated. Results: Among the 20 cases of leukoplakia group, 6 cases showed aneuploidy and 14 showed diploidy. In the 20 cases of OSF group, 2 cases showed aneuploidy and 18 showed diploidy, and in the 20 cases of OSCC group, 10 showed aneuploidy and 10 showed diploidy. Most of the aneuploidy cases showed severe dysplasia. Conclusion: Analysis of DNA ploidy status can serve as a diagnostic tool for early detection of malignancies owing to the subjective nature of traditional histopathological grading.

Background: FxCycleTM Violet (FCV) based flow cytometric (FCM) DNA ploidy analysis is a rapid and simple tool that can substantiate in characterizing the biological behaviour across the spectrum of haematological malignancies and correlates with cytogenetic studies. Materials and Methods: In this prospective study, we performed simultaneous immunophenotyping with FCV based on ploidy analysis in n=132 consecutive new samples, comprising n=110 samples of haemato-lymphoid neoplasms, including acute leukemias (n=67, 60.9%), CML with myeloid blast crisis (n=1, 0.9%), MDS with excess blasts (n=2, 1.8%), mature B cell/ T cell neoplasms (n=37, 33.7%), multiple myeloma (n=3, 2.7%) along with n=22 normal samples. The FCM DNA data was compared with corresponding conventional karyotyping results, wherever available. Results: In FCM ploidy analysis (n=110), the overall DNA index (DI) ranged from 0.81 to 2.17 and S-Phase fraction (SPF) from 0.1-31.6%. Diploidy was seen in n = 90 (81.8%), low-hyperdiploidy in n = 10 (9.1%), high-hyperdiploidy in n = 7 (6.4%) with one case each (0.9% each) having near-tetraploidy, high-hypodiploidy and low-hypodiploidy. The DI of all viable cell populations in normal samples ranged from 0.96-1.05. Conventional karyotyping was performed in n=76/110 cases (70%) with n= 11/76 (15%) culture failures. The modal chromosome number ranged from 45 to 63. A concordance of 95.4% (n=62/65) was noted with corresponding FCM DI. Conclusion: FCV-based ploidy is a sensitive technique that provides complementary information and ascertains a strong correlation with conventional cytogenetics across all haemato-lymphoid neoplasms. It can detect aneuploidy in all B-ALL and myeloma cases, even in hemodiluted samples with cytogenetic culture failure; supplement the diagnoses of erythroleukemia, and provide a useful screen for a higher grade lymph node disease in lymphoma cases with SPF > 3%.

The ability to predict malignant transformation in oral potentially malignant disorders would inform targeted treatment, provide prognostic information and allow secondary prevention. DNA ploidy and loss of heterozygosity assays are already in clinical use, and loss of heterozygosity has been used in prospective clinical trials. This review appraises published evidence of predictive ability and explores interpretation of heterogeneous studies, with different diagnostic methods, criteria and intention. Both methods have a sound biological foundation and have predictive value independent of dysplasia grading and clinical parameters. The application of these two techniques cannot be directly compared because of differences in expression of results and application to populations of different risk. Predicting malignant transformation accurately on an individual patient basis is not yet possible with either technique. However, they are valuable applications to stratify patients for inclusion in trials, identify the lowest risk patients and exclude risk when biopsy results are indeterminate for dysplasia. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer liver metastases (CRLM) has not been identified as a unified disease entity due to the differences in the severity of metastatic disease and tumor aggressiveness. A screen for specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of DNA ploidy, stroma fraction and nucleotyping of initially resectable liver metastases from patients with CRLM. Methods: One hundred thirty-nine consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. DNA ploidy, stroma fraction and nucleotyping of liver metastases were evaluated using automated digital imaging systems. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox regression models. Results: DNA ploidy was identified as an independent prognostic factor for RFS (HR, 2.082; 95% CI 1.053–4.115; P = 0.035) in the multivariate analysis, while stroma-tumor fraction and nucleotyping were not significant prognostic factors. A significant difference in 3-year RFS was observed among the low-, moderate- and high-risk groups stratified by a novel parameter combined with the tumor burden score (TBS) and DNA ploidy (72.5% vs. 63.2% vs. 37.3%, P = 0.007). The high-risk group who received adjuvant chemotherapy had a significantly better 3-year RFS rate than those without adjuvant chemotherapy (46.7% vs. 24.8%; P = 0.034). Conclusions: Our study showed that DNA ploidy of liver metastases is an independent prognostic factor for patients with initially resectable CRLM after liver resection. The combination of DNA ploidy and TBS may help to stratify patients into different recurrence risk groups and may guide postoperative treatment among the patients. [ABSTRACT FROM AUTHOR]

Tobacco use may initiate the process of oral carcinogenesis with clinically undetectable changes. Smoking cessation may prevent its progression. The objective of this study was to evaluate the association between DNA ploidy and micronucleus (MN) frequency in chronic smokers. Three groups were evaluated: Smoker Group, Former Smoker Group and Control Group. Exfoliative cytology was performed on the lateral border of the tongue and mouth floor. MN and DNA ploidy analyses were performed, as well as the correlation between the variables. The data showed a difference between the groups for the total MN (p = 0.0227), and the Smoker group had the highest mean (4.22 ± 4.12). The three groups did not differ statistically from each other on ploidy evaluation (p-value > 0.05). There was also an association between aneuploidy and increased MN frequency in the Former Smoker group (p = 0.0036). In conclusion, these results point out that there is a relationship between the frequency of MN and aneuploidy in former smokers. Moreover, smoking cessation, even for a short period of time, may promote the decrease of MN frequency caused by tobacco use. [ABSTRACT FROM AUTHOR]

Oral leukoplakia (OL) is the most common oral potentially malignant disorder, with a global prevalence of 2%‐3%, variable malignant transformation rate and incompletely understood aetiology. Considering the subjectivity in oral dysplasia grading, other evaluation methods have been tested as predictors of malignant transformation. DNA ploidy status and loss of heterozygosity signatures have been shown to be good predictive markers of malignant transformation. However, effective markers to predict which lesions will progress to invasive carcinoma and by which mechanisms remain unclear. Recent evidence suggests that dysplasia progression to carcinoma occurs through neutral clonal evolution (i.e. randomly). We focus on the genetic basis of OL, encompassing the gross chromosomal alterations and single‐gene mutations, and discuss such alterations in the context of aetiology, clinical presentation and progression. The deeper we understand the genetic basis of OL, the more we approach a better comprehension of the complex and poorly understood process of oral carcinogenesis. [ABSTRACT FROM AUTHOR]

Purpose: DNA ploidy measurement has earlier been suggested as a potentially powerful prognostic tool in many cancer types, but the role in renal tumors is still unclear. Methods: To clarify its prognostic impact, we analyzed the DNA content of 1320 kidney tumors, including clear cell, papillary and chromophobe renal cell carcinoma (RCC) as well as renal oncocytoma and compared these data with clinico-pathological parameters and patient prognosis. Results: A non-diploid DNA content was seen in 37% of 1276 analyzable renal tumors with a striking predominance in chromophobe carcinoma (74.3% of 70 cases). In clear cell carcinoma, a non-diploid DNA content was significantly linked to high-grade (ISUP, Fuhrman, Thoenes; p < 0.0001 each), advanced tumor stage (p = 0.0011), distant metastasis (p < 0.0001), shortened overall survival (p = 0.0010), and earlier recurrence (p < 0.0001). In papillary carcinoma, an aberrant DNA content was significantly linked to high Fuhrman grade (p = 0.0063), distant metastasis (p = 0.0138), shortened overall survival (p = 0.0010), and earlier recurrence (p = 0.0003). Conclusion: In summary, the results of our study identify a non-diploid DNA content as a predictor of an unfavorable prognosis in clear cell and papillary carcinoma. [ABSTRACT FROM AUTHOR]

Background: Oral potentially malignant disorders are a clinical conundrum as there are no reliable methods to predict their behaviour. We combine conventional oral epithelial dysplasia grading with DNA ploidy analysis to examine the validity of this approach to risk assessment in a cohort of patients with known clinical outcomes. Methods: Sections from diagnostic biopsies were assessed for oral epithelial dysplasia using the WHO grading system, and DNA ploidy analysis was performed using established methods. Patients reviewed for a minimum of 5 years who did not develop oral squamous cell carcinoma were classified as "non‐transforming" cases. Patients that developed oral squamous cell carcinoma ≥ 6 months after the initial diagnostic biopsy were classified as having "malignant transformation." Results: Ninety cases were included in the study. Seventy cases yielded informative DNA ploidy results. Of these 70 cases, 31 progressed to cancer. Oral epithelial dysplasia grading and DNA ploidy status were both significantly associated with clinical outcome (P < 0.05). Severe dysplasia had a hazard ratio of 3.50 (CI: 1.46, 8.45; P = 0.005) compared to cases with mild dysplasia. Aneuploidy had a hazard ratio of 2.09 (CI: 1.01, 4.32; P = 0.046) compared to cases with a diploid/tetraploid status. Receiver operating characteristic analysis gave an area under the curve of 0.617 for DNA ploidy status and 0.688 when DNA ploidy status was combined with dysplasia grading. Conclusion: Our findings suggest that combining dysplasia grading with DNA ploidy status has clinical utility which could be used to develop novel management algorithms. [ABSTRACT FROM AUTHOR]

The combination of DNA ploidy and automatically estimated stroma fraction has been shown to correlate with recurrence and cancer death in colorectal cancer. We aimed to extend this observation and evaluate the prognostic importance of this combined marker in prostate cancer. DNA ploidy status was determined by image cytometry and the stroma fraction was estimated automatically on hematoxylin and eosin stained sections in three tumor samples from each patient to account for tumor heterogeneity. The optimal threshold for low (≤56%) and high (>56%) stroma fraction was identified in a discovery cohort (n = 253). The combined marker was validated in an independent patient cohort (n = 259) with biochemical recurrence as endpoint. The combined marker predicted biochemical recurrence independently in the validation cohort. Multivariable analysis showed that the highest risk of recurrence was observed for patients with samples that had both non‐diploid ploidy status and a high stroma fraction (hazard ratio: 2.51, 95% confidence interval: 1.18–5.34). In conclusion, we suggest the combination of DNA ploidy and automatically estimated stroma fraction as a prognostic marker for the risk stratification of prostate cancer patients. It may also be a potential generic marker as concurrent results have been described in colorectal cancer. What's new? The stroma that surrounds tumor cells can have significant effects on tumor growth and behavior. Another hallmark of cancer is aneuploidy caused by genomic instability, which offers an important prognostic marker in several cancer types. In this study, the authors found that combining these two markers—stromal fraction and DNA ploidy—provided a significant predictor of biochemical recurrence in prostate cancer. The low cost, high throughput, and accuracy of digital analysis using this combined method thus promise to provide improved prognostic biomarkers in prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Methods to analyze progression of carcinogenesis and stage of cancer are vital nowadays due to the high prevalence of these lesions. DNA ploidy analysis is one such important method in early diagnosis and improving prognosis. Aims and Objectives: The aim of this study was to correlate histopathological grading and DNA ploidy in oral leukoplakia, oral submucous fibrosis (OSMF), and oral squamous cell carcinoma (OSCC) cases. Materials and Methods: Our study included 80 subjects, grouped into 4 groups of 20 each of OSCC, leukoplakia, OSMF, and healthy individuals. Histopathological grading was carried out in study cases, DNA ploidy was estimated using flow cytometry, and both the findings were correlated. Results: Among the 20 cases of leukoplakia group, 6 cases showed aneuploidy and 14 showed diploidy. In the 20 cases of OSF group, 2 cases showed aneuploidy and 18 showed diploidy, and in the 20 cases of OSCC group, 10 showed aneuploidy and 10 showed diploidy. Most of the aneuploidy cases showed severe dysplasia. Conclusion: Analysis of DNA ploidy status can serve as a diagnostic tool for early detection of malignancies owing to the subjective nature of traditional histopathological grading. [ABSTRACT FROM AUTHOR]

Potato harbors great amount of diversity in terms of its ploidy. The progress of breeding programme is often limited by the hybridization barriers confronted due to differences in ploidy. Hence, understanding the DNA ploidy is of prime importance. The DNA ploidy can be estimated using flow cytometry. Great choices of nuclear isolation buffers (NIB) are available for sample preparation in flow cytometry. Selecting the best suitable among them is critical and also govern the success of experiment. Here, we tested five modified NIBs to identify the best suitable one for potato sample preparation. Investigation reveals best suitability of modified HPI buffer for flow cytometry in potato. The same buffer was used to estimate the genome size and ploidy of randomly selected potato samples. [ABSTRACT FROM AUTHOR]

Background: It was tested whether the difference in carcinogenesis between noxa and human papillomavirus (HPV)‐driven head and neck squamous cell carcinoma (HNSCC) is associated with a variation in genomic instability. Methods: Conventional and molecular cytogenetics in HPV‐positive and HPV‐negative HNSCC cell lines. Results: Numerical aneuploidy determined by multicolor fluorescence in situ hybridization and DNA ploidy was very similar for both entities with most chromosomes being present either in quadruplicate or triplicate, and only few are still diploid with, however, a striking similarity in the overall pattern. A clear difference was seen concerning the translocations formed, with no difference in the total amount but with a significantly higher genomic instability of HPV‐positive cell lines at chromosome 3 as compared to HPV‐negative cells. Conclusion: The different processes of carcinogenesis of HPV‐positive and HPV‐negative HNSCC appear to result in a similar pattern of numerical but a clear difference in structural chromosomal aberrations. [ABSTRACT FROM AUTHOR]

It is believed that the majority of oral cancers develop from oral potentially malignant lesions (OPML). Though they can be easily detected during screening, risk stratification is difficult. During screening clinicians often find it difficult to distinguish OPMLs from benign lesions, and predicting OPML at risk of malignant transformation is particularly challenging. DNA aneuploidy has been known to be a marker of malignancy in a number of sites including the oral cavity. We performed a systematic review to evaluate the effectiveness of DNA-ICM using brushings in differentiating OPMLs from benign/inflammatory lesions during screening and in predicting malignant transformation. MEDLINE, Pubmed, EMBASE electronic databases were systematically searched using a combination of keywords and subject headings. A total of 11 articles satisfied our inclusion criteria. These studies reported a wide range of sensitivity (16-96.4%) and specificity (90-100%) due to the differences in study design, definitions of high risk or low risk lesions and DNA-ICM protocol used. No long-term longitudinal studies were identified to assess the role of DNA-ICM using brushings in predicting malignant transformation. No studies evaluated the role of DNA-ICM in community screening settings. A number of studies combined DNA-ICM with other techniques like cytology or argyrophilic nucleolar organizer region counts leading to improved test results. In spite of DNA aneuploidy being accepted as a marker of malignancy, there is limited evidence of DNA-ICM using brushings being successful as an adjunct oral cancer screening tool. Longitudinal studies and large community screening studies need to be undertaken to draw stronger conclusion. [ABSTRACT FROM AUTHOR]

Abstract: Background and Objectives: Quantitation of cell DNA content, DNA ploidy, has been established as a research and prognostic technique for decades. A variety of instruments have been used although only a few commercially available systems have established quality assurance and published outcome data. The aim of this study was to compare two automated systems. Methods: Nuclear monolayers were obtained from 112 oral biopsies by enzyme digestion and Feulgen staining. These were scanned on both the Fairfield and the Ploidy Work Station (PWS) systems. The overall ploidy diagnosis, number of epithelial nuclei, coefficient of variation (CV) and 5c exceeding rate (5CER) were compared by quantile–quantile plots, t test, Wilcoxon and Spearman's tests. Results: The PWS system identified more nuclei (p < 0.0001) at a lower CV (p < 0.0001). Using the PWS system, fewer samples were classified as indeterminate. No difference between 5CER was found between systems (p > 0.54). There was complete concordance between the two systems in terms of DNA ploidy diagnosis. Conclusions: The PWS system is comparable to the Fairfield system for determination of DNA ploidy and has advantages that may lead to improved performance. [ABSTRACT FROM AUTHOR]

Background: Epithelioid hemangioendothelioma (EHE) involving serous effusion is extremely rare, and the diagnosis can be challenging. DNA ploidy quantitation of EHE in effusion fluids has not been previously described in the English-language literature. Methods: Specimens of cytological diagnosed with EHE in effusion fluids between 2002 and 2009 were retrieved from the pathology files at MD Anderson Cancer Center. A total of four cases of EHE involving or arising from effusion fluids were found, and we reviewed cytospin, smears, cell block sections, and immunostained slides. DNA image analysis for ploidy and proliferation evaluation was performed on a destained, papanicolaou-stained slide from each case. Results: The tumor cells were epithelioid with prominent cytoplasmic vacuolization and intracytoplasmic inclusions, which could resemble reactive mesothelial cells, mesothelioma, or adenocarcinoma. The tumor cells were positive for endothelial markers. DNA image analysis in three of the four cases revealed predominantly diploid and tetraploid subpopulations, with few aneuploid cells and fairly low proliferation indices, and these patients had fairly prolonged survival. Conclusions: DNA image analysis is useful for differentiating EHE from reactive mesothelial cells and high-grade carcinoma. For accurate diagnosis of EHE in effusion fluids, cytologic features should be considered together with clinical history and ancillary studies. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of an automated DNA‐image‐cytometry system as a tool to detect cervical carcinoma. Methods: Of 384 liquid‐based cervical cytology samples with available biopsy follow‐up were analyzed by both the Imager System and a high‐risk HPV test (Cobas). Results: The sensitivity and specificity of Imager System for detecting biopsy proven high‐grade squamous intraepithelial lesion (HSIL, cervical intraepithelial neoplasia [CIN]2‐3) and carcinoma were 89.58% and 56.25%, respectively, compared to 97.22% and 23.33% of HPV test but additional HPV 16/18 genotyping increased the specificity to 69.58%. The sensitivity and specificity of the Imager System for predicting HSIL+ (CIN2‐3+) lesions among atypical squamous cells of undetermined significance samples were 80.00% and 70.53%, respectively, compared to 100% and 11.58% of HPV test whilst the HPV 16/18 genotyping increased the specificity to 77.89%. Among atypical squamous cells‐cannot exclude HSIL, the sensitivity and specificity of Imager System for predicting HSIL+ (CIN2‐3+) lesions upon follow up were 82.86% and 33.33%%, respectively, compared to 97.14% and 4.76% of HPV test and the HPV 16/18 genotyping increased the specificity to 19.05%. Among low‐grade squamous intraepithelial lesion cases, the sensitivity and specificity of the Imager System for predicting HSIL+ (CIN2‐3+) lesions were 66.67% and 35.71%%, respectively, compared to 66.67% and 29.76% of HPV test while HPV 16/18 genotyping increased the specificity to 79.76%. The overall results of imager and high‐risk HPV test agreed in 69.43% (268) of all samples. Conclusions: The automated imager system and HPV 16/18 genotyping can enhance the specificity of detecting HSIL+ (CIN2‐3+) lesions. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is the most frequently occurring malignant tumour in the oral cavity. OSCC arises because of multiple genetic alterations. Cell cycle aberrations and aneuploidy are reportedly among the main characteristics of cancer cells and are associated with aggressive growth and poor prognosis.Methods: The study sample included 47 non-metastasised and 39 metastasised primary OSCC, with matched positive cervical lymph nodes and 17 normal oral mucosa samples. Tissue microarrays (TMAs) were prepared with a minimum of three cores from each case. TMA sections were cut and immunostained with MCM2, Ki-67, geminin and cyclin D1 antibodies. DNA image analysis was performed on the whole tissue section before TMAs were created.Results: The results revealed that there were no differences in cell cycle protein expression in different areas of the tumours or between the metastatic and non-metastatic carcinomas. None of the cell cycle proteins showed significant differences between the lymph node metastasis and the primary OSCC, except for Ki-67. Geminin/Ki-67 ratio showed significant difference between metastatic and non-metastatic tumours. Aneuploidy was detected in all (100%) cases of OSCC. Similarly, all lymph node samples (39 cases) were aneuploid.Conclusion: The results suggest that although there was dysregulation of cell cycle regulatory proteins, only Ki-67 and the MCM2/Ki-67 and geminin/Ki-67 ratios may have prognostic significance in oral cancer. DNA ploidy alone was not specific and may not be a good tool to evaluate prognosis or metastatic progression in oral cavity carcinomas. [ABSTRACT FROM AUTHOR]

Objective We sought to determine whether DNA ploidy correlates with the four molecular subgroups of endometrial carcinoma (EC) as determined using ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). Methods 90 cases of EC previously characterized by clinicopathological parameters, outcomes, and ProMisE molecular subgroup ( POLE EDM, MMR-D, p53 wt or p53 abn) were assessed for DNA ploidy using image cytometry. Associations of ploidy with traditional clinicopathological parameters were also tested. Results Abnormal DNA ploidy status differed amongst the ProMisE groups (p < 0.001) and was found in 80.9% (17/21) of p53 abn, 37.0% (10/27) of p53 wt, 28.6% (4/14) of POLE EDM and 14.3% (4/28) of MMR-D. Abnormal DNA content was significantly associated with lower BMI (p = 0.034) and grade 3 tumors (p = 0.001). In the entire cohort, abnormal DNA content was significantly associated with worse progression free survival (p = 0.0094) but not disease specific survival (p = 0.249) or overall survival (p = 0.187). When examining ploidy within each of the ProMisE groups, abnormal DNA content correlated with worse overall survival (p = 0.041) and progression free survival (p = 0.011) in the MMR-D group. No statistically significant relationship was seen in the remaining 3 groups. Conclusion Abnormal DNA ploidy status did correlate with the molecular subgroups of EC; abnormal DNA content was seen in the large majority of p53 abn cases. Abnormal ploidy however was also seen in smaller numbers in the p53 wt, POLE EDM and MMR-D groups; therefore abnormal DNA content was not a specific marker for any one molecular group. The addition of ploidy to the ProMisE molecular categories conferred additional prognostic value within the MMR-D group, which merits further study. [ABSTRACT FROM AUTHOR]

Assessing the nuclear C–DNA content and estimating DNA ploidy in succulent species, such as dragon fruit ( Hylocereus spp., Cactaceae), is a challenging task. Dragon fruit tissues are rich in polysaccharides that are released during the nuclei isolation procedure, inducing the formation of clusters of nuclei and hence leading to inaccurate results. Our flow cytometry protocol for dragon fruit species is simple, rapid and reproducible. Our innovations include: modifications to the nuclear isolation buffer to ‘match’ the cytosol composition of the cells; filtration of the samples instead of centrifugation, thereby preventing co-precipitation of nuclei and polysaccharides; and staining of the nuclei with propidium iodide. DNA ploidy of dragon fruit samples were estimated using a reference standard − either external or internal − with a known ploidy level and a known nuclear DNA content. The best results were obtained using new emerging and actively growing stem tips, which have lower concentrations of polysaccharides and a lower frequency of endopolyploid nuclei, thereby simplifying the nuclei isolation procedure. [ABSTRACT FROM AUTHOR]

The potential prognostic significance of DNA flow cytometric measurements (DNA ploidy and S-phase fraction) in breast cancer remains in dispute. Inconclusive data, primarily due to the lack of consistent standardization and quality control programs, have limited its translation into clinical practice. The aim of the present review, based on the 25-year experience of the Portuguese Institute of Oncology of Lisbon, is to assess the clinical relevance and application of DNA flow cytometry for the prognosis of breast cancer. Overall, data from Portuguese Institute of Oncology of Lisbon indicate that DNA flow cytometry provides significant prognostic information that is biologically relevant and clinically useful for the management of patients with breast cancer. Furthermore, this data has demonstrated the independent value of DNA aneuploidy as a prognostic indicator of poor clinical outcome in various subgroups of patients with early or locally advanced breast cancer at short- and long-term follow-up. Notably, aneuploidy identifies subsets of patients with grade (G)1 or G2 tumours who exhibit a poor clinical outcome. These patients may benefit from adjuvant chemotherapy, particularly those with luminal A and luminal B/human epidermal growth factor-2-negative endocrine-responsive breast cancer. In conclusion, data from Portuguese Institute of Oncology of Lisbon reinforces the clinical importance and utility of DNA flow cytometric analysis, particularly DNA ploidy, in the prognostic assessment and therapeutic planning for patients with breast cancer. [ABSTRACT FROM AUTHOR]

Background: The role of DNA ploidy in genomic instability of cancer cells and prognosis has been described in a number of studies. The role of the centrosome in cell cycle has also been reported. Aim: In this study, we aimed to investigate the correlation between the centrosome and DNA ploidy in breast cancer in a search for a cytologic predictive and prognostic marker. Materials and Methods: Cell prints were prepared from cell culture of mesothelial cells, fibroblast cell line MRC5 and breast cancer cell lines MCF7 and T47D. Indirect immunofluorescence was used with anti-γ-tubulin and centrosomes were quantified using a fluorescence microscope. DNA ploidy was scored with the DNA index analyzed by flow cytometry. Results: The normal mesothelial cells (94% of the cells with one detected centrosome) and MRC5 diploid cells (68% with two centrosomes) were used as quality controls. A correlation between the number of centrosomes and DNA ploidy was found in MCF7 cell lines (64% of the cells with a number of centrosomes ≥ 3). It was not observed in invasive breast cancer samples; however, the frequency of cells with centrosomes ≥ 3 was found to be slightly higher in DNA aneuploid samples than in DNA diploid samples (15% vs 13.3%). Conclusion: Quantification of centrosome appears to be correlated to DNA ploidy in breast cancer cell lines and slightly associated to DNA aneuploidy in invasive breast cancer. Studies analyzing a larger number of samples as well as morphological abnormalities of the centrosome are needed.

Objectives: To evaluate DNA ploidy and S-phase fraction (SPF) in non-Lynch colonic adenocarcinoma, ulcerative colitis (UC), Crohn disease (CD) which are known as risk factors, and colitis. We correlated ploidy and SPF with tumor grading, staging and BRAF expression., Methods: All studied adenocarcinomas have intact mismatch repair genes as proved by immunohistochemistry. All were assessed for ploidy by automated image-based DNA cytometry and histograms were drawn. Immunostaining by anti-BRAF V600E was performed. Diagnostic laparoscopy (DL) was done as a preliminary step for staging GI cancers., Results: there is significant difference in DNA ploidy between groups; 77.5% and 17.5% of aneuploid cases are adenocarcinoma and UC. Groups are compared in terms of 2C, 4C, above 4C DNA content and SPF and significant difference is principally found between adenocarcinoma group and others. In adenocarcinomas, DNA ploidy is significantly correlated with tumor staging and grading. Regarding BRAF expression, there is significant difference between groups; all adenocarcinomas, 83.33% of UC were positive, while all cases of colitis, bilharzial colitis, CD were negative. There is significant relation between BRAF and SPF among all diploid cases including adenocarcinoma, and among non-neoplastic diploid cases. There is direct significant relation between BRAF intensity and adenocarcinoma staging. There is no significant difference between BRAF and ploidy among UC cases, although 75% of aneuploid UC are positive. DL helps in GI cancer staging. Routine laparoscopy before laparotomy, especially in cancers which have equivocal operability helps to avoid unnecessary laparotomies., Conclusion: Based on significant difference in ploidy between adenocarcinoma and UC and between SPF and ploidy, assessment of ploidy by DNA cytometry for UC and other colitis could therefore predict impending malignant transformation before development of colonic dysplasia. Also measuring SPF in adenocarcinoma helps to select patients who could greatly benefit from chemotherapy. DL has vital role in staging GI cancers.

Nos últimos dez anos, grandes mudanças ocorreram no tratamento do MM com a utilização de novas drogas. Frente a estas novas opções de tratamento é essencial reconhecermos parâmetros clínicos ou biológicos que orientem a melhor escolha terapêutica. Mais recentemente foi validado um novo e simples sistema de estadiamento, International Staging System (ISS), baseado nos valores dabeta2 microglobulina e albumina sérica. Os pacientes são classificados em três grupos de risco: Estádio I: beta2M 3,5 g/dl. Mediana de sobrevida de 62 meses; Estádio II: beta2 M 3,5 - < 5,5 mg/l. Mediana de sobrevida 49 meses; Estádio III: beta2 > 5,5 mg/l. Mediana de sobrevida de 29 meses. Atualmente, a citogenética e achados moleculares estão sendo amplamente reconhecidos como fatores de prognóstico. A deleção do cromossomo 13/13q-, translocação t(4;14), deleção p53 e, mais recentemente, a amplificação da banda cromossômica 1q21 estão associadas a prognóstico reservado.Over the last 10 years, great changes have occurred in the treatment of multiple myeloma (MM) due to the use of new drugs. Considering the new options, it is essential to recognize clinical and biological parameters to arrive at the best therapeutic choice. More recently the new International Staging System (ISS) for multiple myeloma was validated which utilizes two straight forward laboratory parameters: the beta2 microglobulin (beta2M) and albumin levels. Stage I: beta2M < 3.5 mg/L and albumin level > 3.5 g/dL with a median survival of 62 months; stage II: beta2M < 3.5 and albumin < 3.5 g/dL or beta2M > 3.5 to < 5.5 g/dL with a median survival of 49 months; stage III: > 5.5 g/dL with a median survival of 29 months. The importance of cytogenetics and molecular features as prognostic factors is being recognized. Deletion of chromosome 13 or 13q, the t(4:14) translocation, p53 deletion and amplification of chromosome band 1q21 are all associated with poor prognosis.

OBJECTIVE: To study the importance of NB84, synaptophysin and AgNOR and explore the quantitative association of these factors with diagnosis and outcome as well as the association between NB84 and AgNOR and other tumor and stromal factors in twenty-eight peripheral neuroblastic tumors. METHODS: We assessed AgNORs, NB84, synaptophysin and several other markers in tumor tissues from 28 patients with primary neuroblastic tumors. The treatment included: surgery for stage 1, chemotherapy and bone marrow transplantation for most of stages 3 and 4. Histochemistry, immunohistochemistry and morphometry were used to evaluate the amount of tumor staining for AgNOR, NB84 and synaptophysin; the outcome for our study was survival time until death due to recurrent neuroblastic tumors. RESULTS: Only stage (pOBJETIVO: Estudar a importância dos marcadores NB84 e AgNOR e explorar as relações quantitativas entre esses marcadores com o diagnóstico e prognóstico assim como as relações entre NB84 e AgNOR e outros marcadores tumorais e estromais em 28 tumores neuroblásticos periféricos. MÉTODOS: Examinamos AgNOR, NB84 e sinaptofisina e vários outros marcadores em tecidos tumorais de vinte e oito pacientes com tumors neuroblásticos primários. Tratamento dos pacientes incluiu: cirurgia para o estágio 1, quimioterapia e transplante de medula óssea para a maioria dos pacientes nos estágios 3 e 4. Utilizamos histoquímica, imunohistoquímica e morfometria para avaliar a intensidade e extensão de expressão do AgNOR, NB84 e sinaptofisina, tendo o prognóstico dos pacientes incluído o tempo de sobrevida até a morte por recurrência dos tumores neuroblásticos. RESULTADOS: Estadiamento (p