Search

Uterine smooth muscle tumors of unknown malignant potential [STUMP]s are neoplasms with pathological features that preclude an equivocal diagnosis of leiomyosarcoma, but that do not fulfill the criteria for leiomyoma or its variants, and raise concerns that the tumors may behave in a malign fashion. Total hysterectomy with or without bilateral salpingo-oophorectomy is the standard treatment if fertility is completed, whereas myomectomy alone can be taken into consideration in young patients who desire to preserve childbearing potential. A careful surveillance every 6 months for 5 years and then yearly is strongly warranted. Patients with STUMP can relapse as either STUMP or leiomyosarcoma in approximately 11–13% of the cases, and their 5-year overall survival ranges from 92 to 100%. The present paper reviews the clinicopathological features of uterine STUMPs with a particular focus on most commonly accepted histopathological criteria for the diagnosis and on biological behaviour of these controversial neoplasms. • Pathological features of STUMPs preclude an equivocal diagnosis of leiomyosarcoma, but do not fulfill criteria for leiomyoma. • Genomic index seems to represent a prognostic tool for predicting the clinical outcome of patients with STUMPs. • Surgery is the standard therapy of STUMPs, whereas there is no role for adjuvant hormone therapy or chemotherapy. • The recurrence rate of STUMPs ranges between 0% and 36%, with a mean value of approximately 13%. • STUMP can relapse as either STUMP or leiomyosarcoma [ABSTRACT FROM AUTHOR]

Abstract: Objective: In the present study we have examined the pattern of expression of the full length estrogen receptor β (ERβ1) and two ERβ splice variant isoforms (ERβ2, ERβ5) in well-characterized advanced serous ovarian cancers. Methods: Immunohistochemistry was performed with ERβ1, ERβ2, and ERβ5 antibodies and results were correlated with pathological and clinical follow-up data. Expression of ERβ isoforms in a panel of ovarian cancer cell lines and human tumor xenografts was also assessed. Results: Immunohistochemical staining revealed cellular compartment-specific distribution for each isoform in malignant ovarian tissues exhibiting both nuclear staining and cytoplasmic staining. Patients with cytoplasmic ERβ2 expression had significantly worse outcome (p=0.006 at the multivariate analysis), the 5-year survival rate being nearly 28% for patients who did express cytoplasmic ERβ2, and 60% in negative patients. Cytoplasmic ERβ2 expression was also found to be significantly associated with chemoresistance. In concordance with clinical results both nuclear and cytoplasmic expressions were observed for the three isoforms in the cancer cell lines and human tumor xenografts tested. Conclusions: This is the first study to uncover an unfavorable prognostic role of ERβ2 in advanced serous ovarian cancer. If anomalies of ERβ2 cytoplasmic expression could be demonstrated to represent an independent unfavorable prognostic marker and/or a marker predicting chemoresistance in advanced serous ovarian cancer, its immunohistochemical assessment at the time of surgery, could help to recognize candidates for clinical trials of new interventions. [Copyright &y& Elsevier]

Abstract: Objective: In this study we investigated the prognostic value of estrogen receptor α (ERα), ERβ and progesterone receptor (PR) expression in 58 untreated advanced serous ovarian cancer patients. The study also included 12 macroscopically and histopathologically normal ovaries. Materials and methods: Protein expression was evaluated by immunohistochemistry, and antibody staining detected in both the nuclear and cytoplasmic compartments was taken into account. Immunopositivity was analyzed in relation to tumor clinicopathological variables, disease-free survival (DFS), and overall survival (OS). Results: Epithelial cells in ovarian cancer tissue showed significantly lower levels of nuclear ERβ and PR, but not ERα, than in normal ovarian tissue. In the case of ERβ, however, while normal ovarian epithelium exhibited almost exclusively strong nuclear staining, ovarian cancer tissue mostly showed cytoplasmic immunopositivity. Nuclear ERα and ERβ expression were not associated with clinical outcome. Conversely, any cytoplasmic ERβ expression was an independent unfavorable prognostic factor for DFS, a finding approaching statistical significance also for OS. These data suggest that, in advanced serous ovarian cancer, cytoplasmic ERβ signaling may be more important for patient survival than its nuclear signaling. In the case of PR, positivity was an independent favorable prognostic factor for DFS. Conclusions: These novel findings, that need to be confirmed in a large prospective trial, suggest that additional prognostic, and possibly therapeutic opportunities may be available in advanced serous ovarian cancer. [Copyright &y& Elsevier]

Abstract: Introduction. : Metastatic involvement of the mediastinal lymph nodes is an extremely uncommon finding in epithelial ovarian cancers. Case report. : A 63-year-old woman was admitted to hospital for dyspnoea due to an anterior mediastinal mass. The surgical biopsy showed a 6-cm metastatic lymph node with a papillary pattern, scattered psammomas and immunoreactivity for WT1, Cytokeratin 7, EMA and negative for E-cadherin, GCFDP-15, Thyroglobulin, Cytokeratin 20, Cytokeratin 5/6, CEA, Vimentin, Calretinin, TTF1. After 20 months a follow-up CT identified an ovarian mass with the same histological pattern and immunoreactivity of the mediastinal nodule. Results. : Immunohistochemistry, especially WT1, is useful in assessing the ovarian origin of an unusual metastasis particularly if it is the first presentation of the disease. [Copyright &y& Elsevier]

The aim of the study was to investigate by immunohistochemistry the expression of cyclooxygenase-2 (COX-2) in a single institutional series of borderline ovarian tumors (BOT). Moreover, to perform a comparative analysis, COX-2 expression was also analyzed in benign and malignant ovarian tumors.Paraffin-embedded sections form 51 BOT, 26 benign, and 37 malignant ovarian tumors were incubated with polyclonal antiserum against COX-2. The results were calculated as the product of the percentage of the immunostained tumor cells by the relative staining score. Cases with immunostaining values of >1 were considered COX-2-positive.Thirty-four (66.7%) of fifty-one BOT were considered as COX-2-positive, and this rate was not significantly different with respect to COX-2 positivity in benign (50.0%) and in malignant (51.3%) ovarian tumors (P value = 0.23). A significantly higher percentage of COX-2 positivity was found in serous (24 of 24, 100%) with respect to mucinous (9 of 26, 34.6%) BOT (P value = 0.0001). Moreover, 7 (63.6%) of 11 endocervical-type mucinous borderline ovarian tumors were COX-2-positive with respect to only 2 of 15 (13.3%) intestinal-type mucinous BOT (P value = 0.013). The same trend was observed in benign lesions, with COX-2 positivity in 9 of 11 (81.8%) of serous versus 4 of 15 (26.7%) of mucinous tumors (P value = 0.015). On the other hand, no difference was found in the percentage of COX-2 positivity in serous (14 of 29, 48.3%) versus mucinous (5 of 8, 62.5%) ovarian carcinomas (P value = 0.22).COX-2 is differently expressed in BOT according to different histotype. Moreover, an increase of COX-2 positivity was observed from mucinous intestinal BOT to frankly malignant ovarian tumors suggesting that COX-2 overexpression might be involved in mucinous ovarian carcinogenesis. [Copyright &y& Elsevier]

Objective. The expression of the CDK inhibitor p27Kip1 and the extent of endogenous oxidative DNA damage were evaluated in the multistep cervical carcinogenesis.Methods. Archival specimens of low-grade (L) squamous intraepithelial lesions (SILs) (n = 32), high-grade (H) SILs (n = 24) and invasive carcinomas (n = 48) of the cervix were included in the analysis compared with normal cervical squamous epithelium (n =15). Expression level of p27Kip1 was evaluated by immunostaining. Immunohistochemical detection of 8-hydroxydeoxyguanosine (8-OHdG) was considered as marker of oxidative DNA damage in the same tissues.Results. p27Kip1 was constantly expressed in normal epithelium with a mean percentage of positive cells higher than 50%. A progressive significant reduction in the mean percentage of positive cells was observed in L-SIL (18.1%), H-SIL (7.3%) and in invasive carcinomas (2.5%). A progressive significant increase in the levels of 8-OHdG and in the percentage of mean positive cells was observed from L-SIL (2.2%) to H-SIL (12.5%) to invasive carcinomas (25.2%). p27Kip1 and 8-OHdG expression displayed a significant inverse relationship.Conclusions. Expression of p27Kip1 is down-regulated while oxidative DNA damage increases during cervical carcinogenesis. Both parameters are altered at early stages of the process and might help to predict patients at high risk of progression. [Copyright &y& Elsevier]

Over recent years, there has been significant progress in the development of immunotherapeutic molecules designed to block the PD-1/PD-L1 axis. These molecules have demonstrated their ability to enhance the immune response by prompting T cells to identify and suppress neoplastic cells. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes, and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in gynecological malignancies is extremely variable based on tumor stage and molecular subtypes. As a result, a class of monoclonal antibodies targeting the PD-1 receptor and PD-L1, known as immune checkpoint inhibitors, has found successful application in clinical settings. In clinical practice, the standard method for identifying suitable candidates for immune checkpoint inhibitor therapy involves immunohistochemical assessment of PD-L1 expression in neoplastic tissues. The most commonly used PD-L1 assays in clinical trials are SP142, 28–8, 22C3, and SP263, each of which has been rigorously validated on specific platforms. Gynecologic cancers encompass a wide spectrum of malignancies originating from the ovaries, uterus, cervix, and vulva. These neoplasms have shown variable response to immunotherapy which appears to be influenced by genetic and protein expression profiles, including factors such as mismatch repair status, tumor mutational burden, and checkpoint ligand expression. In the present paper, an extensive review of PD-L1 expression in various gynecologic cancer types is discussed, providing a guide for their pathological assessment and reporting. • Immune checkpoint inhibitors targeting PD-1 and PD-L1 found successful applications in clinical settings. • Immunohistochemistry for PD-L1 represents the standard method to select patients for immunotherapy. • PD-L1 expression in gynecologic malignancies is extremely variable, based on tumor stage and molecular subtypes. • Gynecologic cancers have shown variable response to immunotherapy. • PD-L1 expression in different gynecologic malignancies is discussed, with a guide for assessment and reporting. [ABSTRACT FROM AUTHOR]

Abstract: Introduction.: We describe a case of conservatively treated endometrial endometrioid (EE) adenocarcinoma which showed an aggressive clinical outcome after pregnancy. Case.: A 30-year-old woman with a well differentiated EE adenocarcinoma decided to attempt a conservative approach and underwent progestin treatment with subsequent negative ultrasound and hysteroscopic controls. After 3 months, she conceived and at 36 weeks of gestation, a cesarean section was performed with multiple negative biopsies. Eight 8 months after delivery, an exploratory laparotomy documented disseminated poorly differentiated EE adenocarcinoma. Staging work up revealed diffuse metastatic disease. Despite chemotherapy, the patient experienced progression of disease with fatal acute respiratory syndrome due to massive neoplastic pulmonary lymphangitis. Conclusion.: Conservative medical management of endometrial cancer in young women willing to preserve their reproductive potential, carries on potential risks. Careful selection of cases, informed consent, and strict follow up procedures are mandatory. [Copyright &y& Elsevier]

Background. Malignant struma ovarii is a rare tumor, consisting of a struma ovarii with malignant transformation. The association of a malignant struma ovarii with pseudo-Meigs'' syndrome and elevated Ca-125 levels has been never reported.Case. A 66-year-old woman presented with monolateral ovarian mass, ascites, hydrothorax, and elevated Ca-125 levels. Optimal medical staging was performed. Definitive histological examination revealed a malignant struma ovarii. The immediate and complete resolution of symptoms and rapid decline of both Ca-125 and thyroglobulin levels to normal value were achieved post-operatively. After counseling, strict follow-up was planned, and no adjuvant therapy was administered.Conclusion. We report the first case of pseudo-Meigs'' syndrome associated with malignant struma ovarii and elevated Ca-125 levels. The choice of not performing adjuvant therapy is feasible after optimal surgery and adequate staging procedure given to the usually clinical benign course and the low incidence of metastases in malignant struma ovarii. Careful patient counseling is required. [Copyright &y& Elsevier]

Objective Low-grade serous ovarian carcinomas (LGSOCs) are a histological subtype of epithelial ovarian tumors, accounting for fewer than 5% of all cases of ovarian carcinoma. Due to the chemoresistant nature of this subtype a search for more effective systemic therapies is actively ongoing, hormonal therapy showing some degree of activity in this clinical setting. The present study ought to investigate the hormone receptor status of LGSOCs, as a strategy to provide molecular support for patient-tailored hormonal treatments. Methods Estrogen receptor α (ERα), ERβ isoforms (i.e. ERβ1, ERβ2 and ERβ5), progesterone and androgen receptor (PR, AR) expression was evaluated by immunohistochemistry in 25 untreated LGSOC primary tumors, 6 matched metastases and 6 micropapillary variant of serous borderline tumors (micropapillary SBOTs). In vitro cellular models were used to provide insights into clinical observations. Results Our results showed prominent expression of nuclear ERα, ERβ2, ERβ5 and PR in LGSOC primary tissues, while metastatic lesions also exhibit considerable cytoplasmic ERβ2 levels. Notably, a higher expression of ERβ1 protein was determined in micropapillary SBOTs compared to LGSOCs. In vitro experiments on LGSOC cell lines (i.e. HOC-7 and VOA-1056) revealed low/absent ERα, PR and AR protein expression, whereas the three ERβ isoforms were all present. Proliferation of HOC-7 and VOA-1056 was not modulated by either the endogenous or the selective synthetic ligands. Conclusions These novel findings highlight the need of assessing relative levels of ERα and ERβ isoforms in the total receptor pool in future clinical studies investigating molecular predictors of response to hormonal therapy in LGSOC. [ABSTRACT FROM AUTHOR]

The aim of this study is to assess the clinical reproducibility and the potential oncological validity of the molecular information provided by the immunohistochemistry (IHC) to properly stratify the endometrial cancer patients. Retrospective IHC analyses were conducted in a large series of 778 pre-operative uterine-confined ECs, studying the presence/absence of MLH1, MSH2, MSH6 and PMS2 to define the mismatch repair (MMR) stable or instable phenotype; the presence of p53 mutations and other molecular features. The molecular profile was correlated with histological, clinical and prognostic data. Based on IHC assessment , we defined 3 EC populations: stable MMR patients (MMRs), instable patients (MMRi) and p53 mutated patients (p53+). Our result demonstrated that the IHC stratification statistically correlated with the most relevant pathologic-clinical features: FIGO stage (p < 0.001), grading (p < 0.001), histotype (p < 0.001), presence of LVSI (p < 0.001), myometrial invasion and tumor dimension (p = 0.003 for both). These 3 IHC populations statistically reflected the EC risk class ESGO-ESMO-ESP classification 2021 (p < 0.001). These results were also confirmed in the Kaplan-Meier curves in terms of overall survival (OS) and disease-free survival (DFS) (p < 0.0001). The multivariate analyses demonstrated that absence of estrogen receptor (ER) impacted the OS (p = 0.011) and, the Age > 60 years and the ER-status the DFS (p = 0.041 and p = 0.004). In this large series , we demonstrated that the pragmatic and systematic use of IHC may have an important role to properly stratify, in terms of histological features and clinical outcomes, the EC patients. • The aim of the study is to assess the oncological validity of IHC to properly stratify the endometrial cancer patients (EC). • The IHC statistically stratifies EC patients according to the most relevant pathologic-clinical and survival outcomes. • The systematic use of IHC properly stratifies, in terms of histological features and clinical outcomes, the EC patients. [ABSTRACT FROM AUTHOR]

The 2020 ESGO/ESTRO/ESP guidelines stratify the prognosis of endometrial carcinoma (EC) patients combining The Cancer Genome ATLAS (TCGA) molecular signature and pathological factors, including lymphovascular space invasion (LVSI). However, little is known about the prognostic independence of LVSI from molecular signature. To assess whether the prognostic value of LVSI is independent from the TCGA signature. A systematic review and meta-analysis was performed by searching 5 electronic databases from their inception to March 2021. All peer-reviewed studies reporting assessing LVSI as a prognostic factor independent from the TCGA groups in EC were included. Multivariate HRs with 95% confidence interval (CI) were pooled separately for overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). The absence of LVSI was considered as a reference. In DFS analyses, locoregional and distant recurrence were separately considered for one study. Six studies with 3331 patients were included in the systematic review and three studies with 2276 patients in the meta-analysis. LVSI showed a pooled multivariate HR of 1.818 (CI 95%, 1.378–2.399) for OS, 1.849 (CI 95%, 1.194–2.863) for DSS, 1.377 (CI 95%, 1.008–1.880) for DFS excluding one study, 1.651 (CI 95%, 1.044–2.611) for DFS additionally considering locoregional recurrence from one study, and 1.684 (CI 95%, 1.05–2.701) for DFS additionally considering distant recurrence from the same study. LVSI has a prognostic value independent of TCGA signature, as well as age and adjuvant treatment, increasing the risk of death of any cause, death due to EC and recurrent or progressive disease by 1.5–2 times. • The 2020 ESGO/ESTRO/ESP guidelines stratify EC prognosis combining TCGA signature and pathological factors, including LVSI. • However, little is known about prognostic independence of LVSI from TCGA signature. • We aimed to assess whether the prognostic value of LVSI is independent from the TCGA signature. • LVSI has a prognostic value independent of TCGA signature, as well as age and adjuvant treatment. • LVSI increases the risk of death of any cause, death due to EC and recurrent or progressive disease by 1.5–2 times. [ABSTRACT FROM AUTHOR]

Ovarian endometrioid carcinoma (OEC) shares morphological and molecular features with endometrial endometrioid carcinoma (EEC). Several studies assessed the four TCGA groups of EEC, i.e. POLE-mutated (POLEmut), mismatch repair-deficient (MMRd), no specific molecular profile (NSMP) and p53-abnormal (p53abn), in OEC; however, it is unclear whether the TCGA groups have the same distribution and clinicopathological features between OEC and EEC. To assess the distribution and clinicopathological features of the TCGA groups in OEC. A systematic review and meta-analysis was carried out by searching 7 electronic databases from January 2013 to April 2021 for studies assessing the TCGA classification in OEC. Prevalence of each TCGA group in OEC and of FIGO grade 3 and stage>I was pooled using a random-effect model. Prevalence of TCGA groups was compared between OEC and EEC, extracting EEC data from a previous meta-analysis. Kaplan-Meier and Cox regression survival analyses were performed for progression-free survival (PFS). A significant p -value<0.05 was adopted. Four studies with 785 patients were included. The frequency of the TCGA groups in OEC vs EEC was: POLEmut = 5% vs 7.6% (p = 0.594); MMRd = 14.6% vs 29.2% (p < 0.001); p53abn = 14% vs 7.8% (p = 0.097); NSMP = 66.4% vs 55.4% (p = 0.002). The pooled prevalence of FIGO grade 3 was: POLEmut = 19.2%; MMRd = 18.3%; p53abn = 38.1%; NSMP = 14.5%. The pooled prevalence of FIGO stage >I was: POLEmut = 31.6%; MMRd = 42.8%; p53abn = 48.5%; NSMP = 24.6%. Two-, 5- and 10-year PFS was: POLEmut = 100%, 100%, and 100%; MMRd = 89.1%, 82.2% and 73.3%; p53abn = 61.7%, 50.2% and 39.6%; NSMP = 87.7%, 79.6% and 65.5%. The hazard ratio for disease progression (reference = NSMP) was: POLEmut = not estimable (no events); MMRd = 0.825 (p = 0.626); p53abn = 2.786 (p = 0.001). The prognostic value of the TCGA groups was similar between OEC and EEC, despite the differences in the frequency and pathological features of each group. • The TCGA groups differ in distribution and pathological features between ovarian and endometrial endometrioid carcinoma. • The prognostic value of the TCGA groups appears similar between ovarian and endometrial endometrioid carcinoma. • The TCGA groups might be used to guide the management of ovarian endometrioid carcinoma. [ABSTRACT FROM AUTHOR]

Abstract: Objectives. : Alterations of the β subunit of tubulin have been reported to be predictive of resistance to radiation and antitubulin agents in several solid tumors. The aim of the study was to investigate the clinical role of β III tubulin expression as prognostic factor for survival and as a predictive parameter of response to preoperative radiochemotherapy in a single institutional series of locally advanced cervical cancer (LACC) patients. Methods. : The study included 98 LACC patients admitted to the Gynecologic Oncology Unit, Catholic University of Rome and Campobasso between January 1998 and January 2005. Immunohistochemistry was performed by using the polyclonal rabbit anti-β III tubulin antibody (Covance, Princeton, NJ, USA). The value of 10% immunostained tumor cells was arbitrarily chosen as cut-off value to distinguish cases with high versus low β III tubulin content. Results. : In the whole series, β III tubulin immunoreaction was detectable in 66/98 cases (67.3%), and the percentage of positively stained cells ranged from 0 to 100% (median=10%). The percentages of cases with high β III tubulin expression were shown not to be differently distributed according to clinico-pathological characteristics. There was no statistically significant difference in the distribution of cases with high β III tubulin expression according to clinical and pathological response to treatment. During the follow-up period, recurrence and death of disease occurred in 15 and 13 cases, respectively. There was no difference in disease-free and overall survival in cases with high versus low β III tubulin expression. Conclusions. : The assessment of class III β tubulin status seems of little usefulness in order to identify LACC patients with poor chance of response to concomitant radiochemotherapy and unfavorable prognosis. [Copyright &y& Elsevier]

The aim of the study was to analyze the accuracy, the positive and negative predictive values, the specificity, and the sensitivity of the pelvic node frozen section examination in endometrial (EC) and cervical cancer (CC) patients. An accurate evaluation of the results of the frozen section examination in patients submitted to neoadjuvant treatments (chemotherapy and radiochemotherapy), and a comparison between specialist and general pathologist results were performed.A total of 186 consecutive patients with endometrial [52 cases (27.9%)] and cervical [134 cases (72.1%)] cancer underwent surgery at our Department between January 2000 and September 2003. All patients underwent a systematic pelvic lymphadenectomy. While all definitive diagnosis were primarily performed or secondarily revised by the specialist pathologist, the frozen section examination was performed in 65 (35%) cases by the specialist pathologist and in 121 (65%) cases by a general pathologist.Two thousand seven hundred eighteen out of a total of 6710 pelvic lymph nodes, which underwent a definitive histological analysis, were also analyzed at intraoperative frozen section examination. In our series, we observed 10 false negative and five false positive cases. Six out of the 10 (60%) false negative cases and two out of the five (40%) false positive were found in the neoadjuvant treated cervical cancer patients. In this subgroup, five out the six (83.3%) false negative and the two false positive diagnoses were made by the general pathologist, while the specialist pathologist registered only one false negative diagnosis.Intraoperative examination of pelvic lymph nodes during surgery for endometrial and cervical cancer can be considered a safe procedure in the presence of an expert gynecologic oncological team, and can be safely performed in patients submitted to neoadjuvant treatments. [Copyright &y& Elsevier]

In the ESGO/ESTRO/ESP guidelines for endometrial carcinoma management, the risk category of clear cell carcinoma (CCC) is not well defined. In fact, while p53-abnormal (p53abn) CCC are known to be aggressive, the prognosis of mismatch repair-deficient (MMRd) and p53-wild-type (p53wt) CCCs is less clear. To assess the prognostic value of the MMRd and p53wt groups in CCC through a systematic review and meta-analysis. Electronic databases were searched from their inception to February 2021. All studies reporting p53 expression, MMR proteins expression and survival outcomes in endometrial CCC (either pure or mixed) were included. Kaplan-Meier and Cox regression survival analyses with hazard ratio (HR) for overall survival (OS) were performed by using the p53abn group as reference; a significant p -value<0.05 was adopted. Six studies with 136 CCC (114 pure and 22 mixed) were included. Five-year OS was 95.7 ± 4.3% in the MMRd group, 48.4 ± 8.4% months in the p53wt group and 40.6 ± 10.4% in the p53abn group. The hazard of death was significantly lower in the MMRd group than in the p53abn group (HR = 0.062; p = 0.007), while it did not significantly differ between the p53wt and the p53abn group (HR = 0.673; p = 0.222). The POLEmut group could not be analyzed due to the absence of deaths. Similar results were observed in the pure CCC and mixed CCC subgroups. MMRd CCCs seem to have a favorable prognosis and might be lumped together with MMRd endometrioid carcinoma for management purpose. On the other hand, p53wt CCCs appear prognostically more similar to p53abn CCCs. • The prognosis of mismatch repair-deficient (MMRd) and p53-wild-type (p53wt) clear cell carcinoma (CCC) is not well defined • We aimed to assess the prognostic value of the MMRd and p53wt groups in CCC • This may be the first systematic review and meta-analysis assessing the prognostic value of the TCGA groups in endometrial CCC • MMRd CCCs have a favorable prognosis and might be lumped together with MMRd endometrioid carcinoma for management purpose • P53wt CCCs appear prognostically more similar to p53abn CCCs. with a 5-year overall survival <50% [ABSTRACT FROM AUTHOR]

Lymph vascular space involvement (LVSI) is one of the most important prognostic factors in early stage cervical cancer. Its qualitative evaluation represents a milestone for patient risk stratification and treatment choice, but a semi-quantitative analysis of LVSI may offer a more truthful risk model, as already demonstrated for endometrial cancer. The present study aims to investigate the performances of a semi-quantitative evaluation of LVSI in terms of patient risk assessment. In this retrospective study were enrolled patients underwent surgical treatment for early cervical cancer from January 2009 to October 2018. A semi-quantitative evaluation such as the "three-tiered approach" was used to classify the LVSI pathway: negative vs. focal vs. diffuse. Diffuse LVSI was found to be a risk factor for lymph node metastasis (OR: 9.844, p < 0.001), and parametrial involvement (OR: 5.566, p < 0.001). Lymph nodal recurrences were more frequent in diffuse LVSI group (LVSI negative vs. focal LVSI p = 0.369; LVSI negative vs. diffuse LVSI p = 0.002; Focal LVSI vs. diffuse LVSI p = 0.214); and so distant recurrences (LVSI negative vs. focal LVSI p = 0.623; LVSI negative vs. diffuse LVSI p = 0.002; Focal LVSI vs. diffuse LVSI p = 0.026). Patients with diffuse LVSI showed a worse disease-free survival (DFS) than patients with focal or absent involvement (DFS LVSI negative vs. focal LVSI p = 0.938; LVSI negative vs. diffuse LVSI p < 0.001; focal LVSI vs. diffuse LVSI p = 0.036). Semi-quantitative evaluation of LVSI may be useful to identify risk patients for shorter disease-free survival and lymphatic and distant recurrences in patients with early stage. • In Early stage Cervical cancer, diffuse Lymph Vascular Space Involvement (LVSI) are a risk factor for lymph node metastasis. • Patients with diffuse LVSI show a worse disease-free survival (DFS) than patients with focal or absent involvement. • Lymph nodal and distant recurrences are more frequent in patients with diffuse LVSI. [ABSTRACT FROM AUTHOR]

2021 ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma (EC) encourage molecular classification and propose a new prognostic risk stratification based on both pathologic and molecular features. Although deep myometrial invasion (DMI) has been considered as a crucial risk factor in EC, it is unclear if its prognostic value is independent from The Cancer Genome ATLAS (TCGA) groups. To assess if the prognostic value of DMI is independent from the TCGA groups in EC patients. A systematic review and meta-analysis was performed by searching through 5 electronic databases, from their inception to March 2021, for all studies that allowed to assess DMI as a prognostic factor independent of the TCGA groups in EC patients. Pooled hazard ratio (HR) of DMI for overall survival (OS) and disease-free survival (DFS) was calculated at multivariable analyses including TCGA groups as a variable. Superficial myometrial invasion (<50% of myometrial thickness) was considered as a reference. In DFS analyses, locoregional and distant recurrence were separately considered for one study. Five studies with 2469 patients were included in the systematic review and 3 studies with 1549 patients in the meta-analysis. Pooled HR of DMI was 1.082 (CI 95% 0.85–1.377; p = 0.524) for OS, 1.709 (CI 95% 1.173–2.491; p = 0.005) for DFS, 1.585 (CI 95% 1.154–2.178; p = 0.004) for DFS additionally considering locoregional recurrence for one study, and 1.701 (CI 95% 1.235–2.344, p = 0.001) for DFS additionally considering distant recurrence for the same study. DMI does not appear as an independent prognostic factor for OS in EC patients; instead, it seems to affect the risk of recurrence independently from the TCGA groups. Further studies are necessary to confirm these findings and to assess the prognostic impact of DMI separately in each TCGA group. • Deep myometrial invasion (DMI) has been considered as a crucial risk factor in endometrial carcinoma (EC). • It is unclear if DMI prognostic value is independent from TCGA molecular groups. • This may be the first systematic review and meta-analysis in the field. • DMI does not appear as an independent prognostic factor for overall survival in EC patients. • DMI seems to affect the risk of recurrence independently from the TCGA groups. [ABSTRACT FROM AUTHOR]

Deficient expression of mismatch repair proteins (MMR) has been suggested to be a predictor of resistance of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EEC) to conservative treatment. To assess the predictive value of MMR immunohistochemistry in patients conservatively treated for AEH and EEC, and to calculate its predictive accuracy. All patients with AEH or EEC conservatively treated with hysteroscopic resection plus progestins in two referral centers from January 2004 to July 2019 were retrospectively assessed. Immunohistochemistry for MMR was ad hoc performed. Study outcomes were: (i) the association of a deficient immunohistochemical expression of MMR with resistance and recurrence of AEH and EEC after conservative treatment, and (ii) the accuracy of MMR immunohistochemistry in predicting the outcome of conservative treatment. Relative risk (RR) for the associations, and sensitivity, specificity and area under the curve (AUC) on receiver operating characteristic curve for the predictive accuracy were calculated. Sixty-nine women, (47 AEH and 22 EEC) were included; deficient MMR expression was observed in 8.7% of cases. Resistance to conservative treatment was more common in MMR-deficient than MMR-proficient cases (33.3% vs 15.9%; RR = 2.1), but with no statistical significance (p = 0.2508). On the other hand, recurrence was significantly more common in MMR-deficient than MMR-proficient cases (100% vs 26.4%; RR = 3.8; p < 0.0001). In predicting recurrence, a deficient immunohistochemical expression of MMR showed sensitivity = 22.2%, specificity = 100%, and AUC = 0.61. Deficient MMR immunohistochemical expression does not imply resistance of AEH/EEC to conservative treatment. On the other hand, MMR-deficiency appears as a highly specific predictor of recurrence of AEH/EEC after initial regression. • AEH and EEC with MMR deficiency previously appeared to be resistant to progestins • MMR-deficiency does not predict resistance of AEH/EEC to hysteroscopic resection plus progestin • MMR-deficiency predicts AEH/EEC recurrence with 100% specificity • In young patients with AEH/EEC, hysteroscopic resection plus progestin might provide a window period to attempt pregnancy • MMR-deficient patients with AEH/EEC should be closely and carefully followed due to the high risk of recurrence [ABSTRACT FROM AUTHOR]

Undifferentiated/dedifferentiated endometrial carcinoma (UEC/DDEC) is a heterogeneous entity, which may show any of the TCGA molecular signatures and loss of the switch/sucrose nonfermentable (SWI/SNF) proteins expression. To assess the clinico-pathological significance of the TCGA molecular groups and SWI/SNF proteins expression in UEC/DDEC, through a quantitative systematic review. Electronic databases were searched for all studies assessing the TCGA molecular groups, i.e. POLE -mutant, mismatch repair-deficient (MMRd), p53-abnormal (p53abn) and no specific molecular profile (NSMP), and/or the SWI/SNF proteins (SMARCA4/BRG1, SMARCB1/INI1, ARID1B) expression in UEC/DDEC. Student t- test, Fisher's exact test and Kaplan-Meier survival analysis with long-rank test were used to assess differences among groups; a p -value<0.05 was considered significant. Eight studies were included in the systematic review. Among the TCGA groups, the mean patient age was significantly higher in the p53abn group than in the NSMP group (p = 0.048). The POLE -mutant group showed advanced FIGO stage (III-IV) significantly less commonly than the NSMP (p = 0.003) and MMRd (p = 0.008) groups, and a significantly better prognosis than the NSMP (p = 0.007), MMRd (p = 0.011) and p53abn (p = 0.045) groups.The SWI/SNF-deficient cases showed a significantly worse prognosis than the SWI/SNF-intact cases (p = 0.010), while no significant differences were found regarding patient age and FIGO stage. Among UEC/DDEC, POLE -mutant cases show good prognosis, while SWI/SNF-deficient cases show poor prognosis. The other TCGA molecular subtypes seem to be characterized by an intermediate biological behaviour. On this account, UEC/DDEC patients might be subdivided into three risk groups based on POLE and SWI/SNF status. Further studies are necessary in this field. • Undifferentiated carcinoma is a heterogeneous group of endometrial tumors. • TCGA subgroups and loss of the SWI/SNF proteins are the most common molecular signatures. • POLE-mutant group harbours a significantly better prognosis. • SWI/SNF-deficient cases show a significantly worse prognosis. [ABSTRACT FROM AUTHOR]

Abstract: Background. : Metastatic bone involvement in vulvar squamous carcinoma is very rare. Here, we present a case of primary adenocarcinoma of the Bartholin''s gland giving rise to isolated skull metastasis. Case. : A 74-year-old woman was referred with a diagnosis of primary vulvar adenocarcinoma of the right labium minus. A right hemivulvectomy was performed with ipsilateral inguinofemoral lymphadenectomy, revealing a primary adenocarcinoma of the Bartholin''s gland and metastatic involvement in 6 out of 13 lymphnodes. During chemotherapy administration, the patient started complaining of a worsening of right hypoacousis. CT scan and MRI of the brain showed the presence of a metastatic lesion on the right side of the skullbone. The diagnosis was metastatic poorly differentiated adenocarcinoma. Conclusion. : In adenocarcinoma of the Bartholin''s gland at an advanced stage of disease, a bone scan or survey in the preoperative as well as follow up staging procedures could be useful. [Copyright &y& Elsevier]

A case of stage IB2 cervical cancer at 27 weeks of pregnancy, treated with neoadjuvant chemotherapy followed by radical Cesarean hysterectomy with full pelvic and infra-mesenteric lymphadenectomy, and adjuvant chemo-radiation is described. While she remains without disease, her baby was diagnosed with acute myelogenous leukemia. We highlight the pre-operative work-up, treatment options, safety, feasibility, and outcomes for the mother and her fetus. [ABSTRACT FROM AUTHOR]

Objective Adult granulosa cell tumor (AGCT) is a rare form of sex-cord stromal ovarian tumors. Due to their origin, AGCTs secrete estrogens, and thus, estrogen receptor (ER)-mediated signaling has been considered as a possible target for therapy. The aim of the present study was to get insights into estrogen receptor status and activity in AGCTs, as a strategy to provide molecular support for personalized hormonal treatments. Methods We evaluated by immunohistochemistry the expression of ERα, ERβ isoforms ( i.e. ERβ1, ERβ2 and ERβ5), progesterone and androgen receptor (PR, AR) in 20 untreated AGCTs and 12 unmatched recurrent lesions. Thereafter, we visualized by immunofluorescence, the subcellular distribution of cytoplasmic receptors, and by the proximity ligation assays (PLA) we characterized in situ their ability to interact with other proteins involved in the apoptotic cascade. Results Primary AGCTs predominantly expressed ERβ isoforms, along with PR and AR, while only 30% of patients showed ERα expression. Recurrent tumors were associated with a decrease in AR levels. From mechanistic studies it emerges that ERβ2, and to a lesser extent ERβ1 and AR, are mitochondrial components in cancer cells and that ERβ2 can act as a binding partner of proteins involved in the apoptotic cascade, in turn potentially inhibiting apoptosis. Conclusions As in other endocrine tumors, ERβ may play a role in the pathogenesis of AGCT; it is crucial to understand estrogen receptor-mediated pathways before planning hormonal treatment strategies in AGCT. [ABSTRACT FROM AUTHOR]

Objective Lysyl oxidase (LOX) is an enzyme that catalyzes the cross-linking of collagen and elastin in the extracellular matrix, thus controlling the tensile strength of tissues. Along with this primary function, there are evidences supporting a role for LOX in many critical biological functions, including gene expression regulation, cell growth, adhesion and migration. Accordingly, recent studies have supported a pivotal role for LOX in cancer progression and metastasis. The current study aimed at investigating the prognostic significance and the functional role of intracellular LOX in ovarian cancer. Methods To this end, we analyzed LOX expression by immunohistochemistry in archived tumor material from advanced high grade serous ovarian cancer (HGSOC) patients ( n = 70) and correlated data with clinicopathological parameters and with response to chemotherapy. In vitro experiments were also used to investigate the functional consequences of LOX expression on behavioral aspects of HGSOC cells. Results Our results showed that nuclear LOX expression is associated with unfavorable outcome in advanced HGSOC, being an independent prognostic factor for disease recurrence. Besides, high nuclear levels were seen to be associated with resistance to first-line chemotherapy. Through gene expression modulation experiments in HGSOC cell lines, we demonstrate that LOX positively regulates cell proliferation, migration and anchorage-independent growth. Conclusions Collectively, our data suggest that LOX functions as a tumor promoter in HGSOC and positively regulates several aspects of the metastatic cascade. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To compare the diagnostic accuracy of ultrasound (US) and magnetic resonance imaging (MRI) in the preoperative assessment of early-stage cervical cancer using pathologic findings as the reference standard. Patients and methods: Prospective multi-center trial enrolling 209 consecutive women with early-stage cervical cancer (FIGO IA2–IIA) scheduled for surgery. The following parameters were assessed on US and MRI and compared to pathology: remaining tumor, size, tumor stromal invasion<2/3 (superficial) or ≥2/3 (deep), and parametrial invasion. Results: Complete data were available for 182 patients. The agreement between US and pathology was excellent for detecting tumors, correctly classifying bulky tumors (>4cm), and detecting deep stromal invasion (kappa values 0.84, 0.82, and 0.81 respectively); and good for classifying small tumors (<2cm) and detecting parametrial invasion (kappa values 0.78 and 0.75, respectively). The agreement between MRI and histology was good for classifying tumors as <2cm, or >4cm, and detecting deep stromal invasion (kappa values 0.71, 0.76, and 0.77, respectively). It was moderately accurate in tumor detection, and in assessing parametrial invasion (kappa values 0.52 and 0.45, respectively). The agreement between histology and US was significantly better in assessing residual tumor (p <0.001) and parametrial invasion (p <0.001) than the results obtained by MRI. Imaging methods were not significantly influenced by previous cone biopsy. Conclusion: US and MRI are highly accurate for the preoperative assessment of women with early-stage cervical cancer, although US may be more accurate in detecting residual tumors and assessing parametrial invasion. [Copyright &y& Elsevier]

Abstract: Objective: To compare the accuracy of preoperative transvaginal sonography (TVS) and intraoperative frozen section (FS) in the assessment of myometrial invasion of endometrial carcinoma, having the definitive histological examination as gold standard. Methods: 155 consecutive women (mean age 63years, range 32–88) diagnosed as having endometrial carcinoma were prospectively evaluated at TVS in order to preoperatively stage the disease. All the patients subsequently underwent complete surgical staging including total abdominal hysterectomy, bilateral oophorectomy, pelvic and lumboaortic lymphadenectomy. After removal of the uterus, intraoperative FS was performed by pathologists with special interest in gynaecologic oncology in a predefined, standardized manner. Sensitivity, specificity, positive and negative predictive values were calculated for both modalities as regards neoplastic invasion of the myometrium. Results: Overall, 131 women (84.5%) had an endometrioid adenocarcinoma, 8 (5.2%) an adenosquamos carcinoma, 7 (4.5%) a serous papillary carcinoma, 4 (2.6%) a clear cell carcinoma, 3 (1.9%) a mixed type carcinoma, 1 (0.6%) a carcinosarcoma, and 1 (0.6%) a mesodermal mixed malignant tumor. Sensitivity, specificity, positive and negative predictive values and accuracy for TVS in the evaluation of myometrial infiltration were: 75%, 89%, 86%, 79% and 81%. Corresponding features for FS were: 92%, 92%, 89%, 94% and 92%. The diagnostic performance of FS was higher than that of TVS (Cohen''s K value: 0.841; p<0.0005). Conclusion: Intraoperative FS performed better than preoperative TVS in the assessment of myometrial invasion by endometrial cancer. Despite being time consuming, FS can be regarded as a useful modality in order to decide whether to perform lymphadenectomy in cases with poor visualization of the endometrium at TVS and when TVS gives inconclusive results. [Copyright &y& Elsevier]

Abstract: Objective: The aim of the study was to investigate the potential clinical relevance of immunohistochemically assessed RON expression in a large, single institution series of primary untreated advanced ovarian cancer patients. Methods: Immunohistochemical analysis was performed by using the polyclonal rabbit anti-RON-β antibody (C-20, clone sc-322, Santa Cruz, California). Results were expressed as the total proportion of immunostained tumor cells (RON positivity), or the percentage of cells showing strong staining of RON expression (H-RON positivity). Results: In the overall series RON positive immunoreaction was observed in 103/141 cases, while H-Ron positivity was detected in 577141 (40.4%) cases. No association between RON and H-RON expression with response to first-line treatment was documented. During the follow up period, progression and death of disease were observed in 111 (78.7%) and 76 (53.9%) cases, respectively. Cases with strong H-RON expression has a shorter overall survival (median=35 months) than cases with low RON levels (median=59 months) (X 2 =−2.1, p value=0.032). In multivariate analysis, only platinum resistance, and extent of residual tumor retained an independent negative prognostic role for OS, with the percentages of H-RON positively immunostained cells showing a borderline statistical significance (p value=0.0643). The unfavourable role of elevated percentages of H-RON expression was maintained only in the subgroup of platinum resistant recurrent ovarian cancer patients (X 2 =3.89, p value=0.048) compared to the platinum sensitive ones (X 2 =1.98, p value=0.16). Conclusions: The assessment of RON expression deserves further attention as a parameter helpful to identify poor prognosis ovarian cancer patients potentially candidates to investigational agents. [Copyright &y& Elsevier]

Abstract: Objective. : No thorough investigation of the diagnostic performance of frozen section analysis in predicting the final status of lymph nodes after exposure to concomitant chemoradiation (CT/RT) has been performed until now. The aim of the study was to analyze the accuracy of pelvic lymph node frozen section examination in a large, consecutive series of locally advanced cervical cancer (LACC) patients undergoing preoperative CT/RT. Methods. : A total of 123 consecutive LACC patients underwent preoperative CT/RT followed by radical hysterectomy according to Piver classification, with bilateral systematic pelvic lymphadenectomy. If pelvic nodes were intraoperatively defined as positive for tumor metastasis, para-aortic lymphadenectomy up to inferior mesenteric artery was carried out. The diagnostic performance of frozen section examination of pelvic lymph nodes was assessed by calculating the negative predictive value (NPV), the positive predictive value (PPV), specificity, sensitivity, and overall accuracy. Results. : A total of 1647 and 4345 pelvic lymph nodes were analyzed by frozen section examination and at final diagnosis, respectively. Lymph node metastases were found in 11 cases (8.9%) at frozen section examination, and in 14 cases (11.4%) at definitive histological diagnosis. We found 7 incorrect diagnoses at frozen section examination, represented by 5 false negative and 2 false positive cases. Specificity, sensitivity, overall accuracy, NPV, and PPV were 98.2%, 64.3%, 94.3%, 95.5% and 81.8%, respectively. Conclusions. : Preoperative chemoradiation does not impair the role of frozen section analysis in predicting the pelvic lymph node involvement in LACC patients. [Copyright &y& Elsevier]

Abstract: Objectives. : Cervical and vulvar cancers develop through well-defined precursor lesions but their exact pathogenesis is still unknown. The dystroglycan complex is a transmembrane glycoprotein that forms a continuous link from the extracellular matrix to the actin cytoskeleton. Deregulated expression of dystroglycan has been reported in human malignancies and related to tumor differentiation and aggressiveness. In this study, expression of dystroglycan was evaluated in the multistep cervical and vulvar tumorigenesis. Methods. : Expression of the dystroglycan complex was evaluated by immunostaining in lesions representing different stages of vulvar and cervical tumorigenesis using a monoclonal antibody which recognizes carbohydratic epitopes on the α-dystroglycan subunit. Results. : α-dystroglycan was constantly detected in normal cervical epithelium with a mean percentage of positive cells higher than 80%. A progressive significant reduction in the mean percentage of positive cells was observed in low (67%) and high grade SIL (14%) and in invasive carcinomas (2.6%) of the cervix. In cancers, no differences were observed in terms of percentage of positive cells when cases were stratified according with either tumor grade or stage. A progressive significant reduction in the mean percentage of positive cells was also observed from normal vulvar epithelium (90%) to VIN1 (66%), VIN2 (28%) and invasive vulvar carcinomas (22%). No significant decrease in the α-dystroglycan staining was observed in squamous cell hyperplasia lesions (85%) while lichen sclerosus displayed a percentage of positive cells (47%) significantly lower than normal epithelium. Conclusions. : Detection of α-dystroglycan is frequently lost in human cervical and vulvar tumorigenesis and further studies are warranted to verify whether evaluation of this molecule might serve as marker of risk progression of preneoplastic lesions and to better understand its significance in terms of cancer development. [Copyright &y& Elsevier]

Abstract: Background.: Malignant transformation may occur in up to 1% of women with endometriosis and only 20% of these cases occur at extragonadal pelvic sites. Similarly, urinary tract endometriosis is rare and occurs in only 1% of all endometriotic lesions. Case.: An endometrioid carcinoma with squamous differentiation arising from periureteral endometriosis presented as a pelvic mass encasing the right ureter. The patient had a history of total hysterectomy and bilateral salpingo-oopherectomy 8 years earlier because of bilateral serous benign cysts with right hemorrhagic corpus luteum and uterine fibroids, and has since been under unopposed estrogen replacement therapy for 5 years. Conclusion.: This is the second case of a malignancy arising in endometriosis presenting as an obstructive ureteral mass and the first case of a patient with this condition whose endometriosis is not consistent with a gonadal origin. An analysis of the case and related literature is presented together with the discussion of possible pathogenetic mechanisms. [Copyright &y& Elsevier]

Abstract: Objective : We aimed at investigating by immunohistochemistry the relationship between cyclooxygenase-2 (COX-2) and estrogen (ER), and progesterone (PR) receptors in a single institution series of 90 primary untreated endometrial cancer patients. The simultaneous assessment of p53 protein, ki67, and neu protein has been carried out. Methods : Immunohistochemistry was performed on paraffin-embedded sections by using rabbit polyclonal antiserum against human COX-2, anti-ER (clone 1D5), and anti-PR (clone 1A6) monoclonal antibodies, anti ki67 (clone MIB-1) and p53 (clone DO-7), and polyclonal antibody anti human c-erbB2/neu. Results : There was no difference in the distribution of COX-2, p53, and neu positive cases according to ER or PR positivity, while the percentage of ki67 positive endometrial tumors was significantly higher in ER negative versus ER positive tumors (54.5% versus 31.6%, P value = 0.044). ER and PR positive tumors showed a statistically significant association with clinicopathological parameters of better clinical outcome. There was no clear association between COX-2 positivity and any of the clinicopathological features. The percentage of ki67, p53, and neu positive tumors was found to be strictly related to more aggressive features. Only advanced stage of disease was found to be a predictor of poor prognosis (P value = 0.034). None of the biological parameters examined was shown to be associated with patient outcome. Conclusions : We showed that COX-2 expression is not correlated with ER, PR, p53, and neu, thus suggesting that COX-2-mediated activities may follow independent pathways. Our findings provide the rationale to design trials based on the combination of antihormones with inhibitors of COX-2 and neu in recurrent/metastatic endometrial cancer. [Copyright &y& Elsevier]

Objective. Cyclooxygenase-2 (COX-2) overexpression has been associated with parameters of tumor aggressiveness and unfavourable clinical outcome in several solid tumors. We investigated by immunohistochemistry the expression of COX-2 in normal vulvar tissue, non-neoplastic vulvar epithelial lesions, vulvar intraepithelial neoplasia (VIN) and invasive vulvar cancer (IVC).Methods. The expression pattern of COX-2 was studied in normal vulvar tissue, in six cases of lichen sclerosus (LS), seven cases of squamous cell hyperplasia (SCH), 20 VIN, 2 Paget''s disease and 36 IVC. The relationship between COX-2 expression and clinicopathologic parameters in IVC patients has been also addressed. Sections were incubated with normal rabbit serum for 15 min, then with rabbit polyclonal antiserum against human COX-2 (Cayman, Ann Arbor, MI, USA). The results were reported as mean ± standard error (SE) of COX-2 integrated density values (IDV).Results. Higher levels of tumor/stroma COX-2 IDV ratio were found in stages III–IV (mean ± SE = 3.5 ± 0.8) than stages I–II disease (mean ± SE = 1.4 ± 0.3) (P value = 0.04). In the subgroup of stage I cases, tumor/stroma COX-2 IDV values were higher in cases with > 1 mm stromal invasion (T1b) than cases with ≤ 1 mm stromal invasion (T1a) (mean ± SE = 1.6 ± 0.3 vs. mean ± SE = 0.6 ± 0.1) (P = 0.033). Moreover, we observed higher tumor/stroma COX-2 IDV in cases with metastatic lymph node involvement than cases without lymph node involvement (mean ± SE = 3.5 ± 0.8 vs. mean ± SE = 1.3±0.4) (P = 0.037).Conclusion. This study suggests that COX-2 overexpression may contribute to vulvar tumorigenesis and progression. Moreover, the correlation of tumor/stroma COX-2 IDV ratio with tumor extension and metastatic lymph node involvement, which represent the major prognostic parameters in this neoplasia, implies that tumor/stroma COX-2 IDV ratio could have a prognostic role in vulvar cancer. [Copyright &y& Elsevier]

: ObjectiveThe aim was to study the effectiveness of subjective color Doppler evaluation and spectral Doppler parameters in preoperative characterization of endometrial carcinomas.: MethodsSeventy-six patients with endometrial carcinoma were preoperatively analyzed by color Doppler ultrasound in order to subjectively evaluate the amount of intratumoral blood flow (color score) and to analyze the lowest resistance index (RI), the highest peak systolic velocity (PV), and the highest time averaged maximum velocity (TAMVX). These parameters were analyzed according to clinico-pathological characteristics.: ResultsIn 13 patients no intratumoral arterial vessels were detected by color Doppler examination. No lymph node metastases were found in this group of patients. Positive nodes were found in 24% of patients with detectable arterial vessels, although the difference did not reach the statistical significance. No differences were found in spectral Doppler parameters (RI, PV, TAMVX) according to tumor characteristics or nodal involvement. A higher percentage of cases with a color score of 3 was found in stage >I than in stage I patients (69 vs 42%, P < 0.05), and in patients with myometrial invasion greater than 50% than in those with less than 50% invasion (72 vs 38%; P = 0.05).: ConclusionNodal metastases were found in 24% of patients with detectable vessels at color Doppler examination. Subjective analysis of vessel density correlated >50%, myometrial invasion, but spectral Doppler analysis was not predictive of surgical stage, tumor grade, myometrial invasion, or lymph node metastases. These results do not support the use of preoperative intratumoral blood flow analysis as a clinical test in evaluating tumor characteristics or in predicting lymph node metastases. [Copyright &y& Elsevier]