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Zannoni G F, Prisco M G, Vellone V G, De Stefano I, Vizzielli G, Tortorella L, Fagotti A, Scambia G & Gallo D (2011) Histopathology 59, 909-917 Cytoplasmic expression of oestrogen receptor beta (ERβ) as a prognostic factor in vulvar squamous cell carcinoma in elderly women Aims: To investigate the prognostic value of cytoplasmic oestrogen receptor beta (ERβ) expression in a series of untreated patients with non-human papillomavirus (HPV)-related vulvar cancer. Methods and results: Immunohistochemistry was carried out using a polyclonal rabbit anti-human ERβ antibody. The nuclear and cytoplasmic expression of ERβ was evaluated in 33 patients. Cytoplasmic immunoreactivity was correlated with histopathological and molecular parameters (Ki67, p21), disease-free survival (DFS) and overall survival (OS). The expression of cytoplasmic ERβ was found to be associated with grade ( P = 0.006), while no association was found with any of the remaining variables examined. Cases with high cytoplasmic ERβ expression showed lower DFS and OS compared to cases with low cytoplasmic ERβ ( P = 0.007, P = 0.01, respectively). There was also a progressive decline in both the DFS and OS with increasing tumour size ( P = 0.05, P = 0.07, respectively) and with increasing depth of infiltration ( P = 0.14, P = 0.07, respectively). On multivariate analysis, only tumour size and cytoplasmic ERβ staining retained an independent negative prognostic role for DFS and OS. Conclusions: The assessment of cytoplasmic ERβ expression could be helpful to identify poor prognosis in elderly patients with non-HPV-related vulvar squamous cell carcinoma (SCC). [ABSTRACT FROM AUTHOR]

Zannoni G F, Prisco M G, Vellone V G, De Stefano I, Scambia G & Gallo D (2011) Histopathology, 265-275 The most common vulvar squamous cell carcinoma (conventional SCC) occurs in elderly women and develops following a human papillomavirus (HPV)-negative pathway. Because the highest incidence of conventional SCC is observed in patients with low oestrogen levels (postmenopausal women), the aim was to investigate whether hormonal factors could play a role in the development of cancer. The expression profile of oestrogen receptor α (ERα), ERβ and progesterone receptor (PR) in a section containing both normal and tumour tissue, as well as the SCC-associated vulvar lesion, was evaluated in 34 elderly patients. Also, as recent studies have identified E-cadherin as a novel transcriptional target of oestrogen signalling, the modulation of this epithelial-mesenchymal transition (EMT) marker was studied. Finally, the expression of the proliferation marker Ki67 and of the apoptotic marker p53 was assessed. Results showed that changes in both ERα and ERβ expression characterize the transition from normal epithelium to cancer in patients with vulvar SCC: ERα was lost in cancer while ERβ decreased, mainly showing cytoplasmic localization. A reduction in the expression of E-cadherin was also observed in tumours, compared to normal epithelium. The data put the ER signalling pathway into the spotlight as a potentially important factor in vulvar carcinogenesis. [ABSTRACT FROM AUTHOR]

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]

Aims: To morphologically and immunophenotypically characterize dedifferentiated uterine leiomyosarcoma (LMS). Methods and results: We identified 23 dedifferentiated uterine LMS, defined as a malignant uterine smooth muscle tumour containing discrete differentiated and dedifferentiated components (i.e. with and without morphologic and immunophenotypic evidence of smooth muscle differentiation, respectively). The differentiated component was leiomyosarcoma in most cases (17/23), though some arose from a leiomyoma (n = 4) or smooth muscle tumour of uncertain malignant potential (n = 2). The dedifferentiated tumour component showed noncohesive polygonal cells with moderate to abundant cytoplasm, pleomorphic nuclei with coarse vesicular to smudged chromatin, one or more macronucleoli, frequent multinucleation, and atypical mitoses. Three cases showed heterologous osteosarcomatous or chondrosarcomatous differentiation. Immunohistochemistry revealed alterations characteristic of uterine LMS, including Rb loss (18/19); strong diffuse p16 (17/19); strong diffuse (9/19) or complete absence of (5/19) p53; and ATRX loss (6/16). Compared to a control cohort of uterine LMS without dedifferentiation, dedifferentiated uterine LMS showed significantly shorter disease‐specific (median, 54 versus 20 months; 5‐year DSS, 46% versus 36%; P = 0.04) and disease‐free (median, 31 versus 8 months; 5‐year DFS, 42% versus 8%; P = 0.002) survival. Of 19 dedifferentiated uterine LMS with follow‐up, 12 had died of disease at median 14 (range, 2–73) months; four were alive with disease at 4, 12, 44, and 50 months; and three were alive with no evidence of disease at 56, 109, and 114 months. Conclusion: Routine prospective recognition of dedifferentiated uterine LMS and distinction from mimics is advocated for accurate prognostication and for further characterisation of these tumours. [ABSTRACT FROM AUTHOR]

We found that the most prevalent subgroups were the CNH subgroup (42.5%) and the CNL subgroup (40.9%), while the MSI subgroup (9.8%) and the POLE subgroup (3.8%) were less common (Figure). In fact, the CNL subgroup (also referred to as the "endometrioid" subgroup) typically includes hormone-responsive, low-grade endometrioid carcinomas, which have a good-to-intermediate prognosis.[1] Conversely, the CNH subgroup (also referred to as the "serous" subgroup) is mainly composed of serous carcinomas and bears the worst prognosis among all TCGA subgroups.[1] Therefore, it might be hypothesized that some CCCs are biologically similar to endometrioid carcinoma and have a better prognosis, while some are similar to serous carcinomas and have a poorer prognosis. Targeted molecular and immunohistochemical analyses of endometrial clear cell carcinoma show that POLE mutations and DNA mismatch repair protein deficiencies are uncommon. [Extracted from the article]

We found that the most prevalent subgroups were the CNH subgroup (42.5%) and the CNL subgroup (40.9%), while the MSI subgroup (9.8%) and the POLE subgroup (3.8%) were less common (Figure). In fact, the CNL subgroup (also referred to as the "endometrioid" subgroup) typically includes hormone-responsive, low-grade endometrioid carcinomas, which have a good-to-intermediate prognosis.[1] Conversely, the CNH subgroup (also referred to as the "serous" subgroup) is mainly composed of serous carcinomas and bears the worst prognosis among all TCGA subgroups.[1] Therefore, it might be hypothesized that some CCCs are biologically similar to endometrioid carcinoma and have a better prognosis, while some are similar to serous carcinomas and have a poorer prognosis. Targeted molecular and immunohistochemical analyses of endometrial clear cell carcinoma show that POLE mutations and DNA mismatch repair protein deficiencies are uncommon. [Extracted from the article]

Introduction: The aim of the current study is to evaluate the detection rate of micro- and macro-metastases of the One-Step Nucleic Acid Amplification (OSNA) compared to frozen section examination and subsequent ultra-staging examination in early stage endometrial cancer (EC). Material and methods: From March 2016 to June 2016, data of 40 consecutive FIGO stage I EC patients were prospectively collected in an electronic database. The sentinel lymph node mapping was performed in all patients. All mapped nodes were removed and processed. Sentinel lymph nodes were sectioned and alternate sections were respectively examined by OSNA and by frozen section analysis. After frozen section, the residual tissue from each block was processed with step-level sections (each step at 200 micron) including H&E and IHC slides. Results: Sentinel lymph nodes mapping was successful in 29 patients (72.5%). In the remaining 11 patients (27.5%), a systematic pelvic lymphadenectomy was performed. OSNA assay sensitivity and specificity were 87.5% and 100% respectively. Positive and negative predictive values were 100% and 99% respectively, with a diagnostic accuracy of 99%. As far as frozen section examination and subsequent ultra-staging analysis was concerned, we reported sensitivity and specificity of 50% and 94.4% respectively; positive and negative predictive values were 14.3% and 99%, respectively, with an accuracy of 93.6%. In one patient, despite negative OSNA and frozen section analysis of the sentinel node, a macro-metastasis in 1 non-sentinel node was found. Conclusions: The combination of OSNA procedure with the sentinel lymph node mapping could represent an efficient intra-operative tool for the selection of early-stage EC patients to be submitted to systematic lymphadenectomy. [ABSTRACT FROM AUTHOR]