Search

Expression of neuroendocrine (NE) markers in primary ovarian non-NE epithelial tumors has rarely been evaluated. The aim of our study was to evaluate the expression of the most widely used NE markers in these neoplasms and to determine any prognostic significance of NE marker expression. The cohort consisted of 551 primary ovarian tumors, including serous borderline tumors, low-grade serous carcinomas, high-grade serous carcinomas (HGSC), clear cell carcinomas, endometroid carcinomas, mucinous borderline tumors, and mucinous carcinomas. Immunohistochemical analysis was performed using antibodies against INSM1, synaptophysin, chromogranin, and CD56 on tissue microarray. Positivity for INSM1, synaptophysin, chromogranin, and CD56 was most frequently observed in mucinous tumors (48.7%, 26.0%, 41.5%, and 100%, respectively). The positivity for these NE markers was mostly restricted to nonmucinous elements distributed throughout the tumor. The mucinous borderline tumor and mucinous carcinomas groups had similar proportions of positivity (mucinous borderline tumor: 53%, mucinous carcinomas: 39%). In the other tumor types, except for HGSC, there was only focal expression (5%-10%) or negativity for NE markers. HGSC showed high CD56 expression (in 26% of cases). Survival analysis was only performed for CD56 in HGSC as this was the only group with sufficient positive cases, and it showed no prognostic significance. Except for mucinous tumors, expression of NE markers in non-NE ovarian epithelial tumors is low. CD56 expression in HGSC occurs frequently but is without diagnostic or prognostic value., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 by the International Society of Gynecological Pathologists.)

In gynecological neoplasms, immunohistochemical (IHC) expression of p53 is generally an accurate predictor of TP53 mutation status if correctly interpreted by the pathologist. However, the literature concerning cut-offs, frequency and prognostic significance of p53 staining in ovarian mucinous tumours is limited and heterogeneous. We performed an analysis of 123 primary ovarian mucinous tumours including mucinous borderline tumours (MBT), mucinous carcinomas (MC), and tumours with equivocal features between MBT and MC. We assessed p53 expression for the three recognised patterns of aberrant staining in ovarian carcinoma [overexpression ('all'), null and cytoplasmic] but using a recently suggested cut-off for aberrant overexpression in ovarian mucinous tumours (strong nuclear p53 staining in ≥12 consecutive tumour cells) and correlated the results with next generation sequencing (NGS) in all qualitatively sufficient cases (92/123). Aberrant p53 expression was present in 25/75 (33.3%) MBT, 23/33 (69.7%) MC (75% of MC with expansile invasion and 61.5% with infiltrative invasion), and 10/15 (66.7%) tumours equivocal between MBT and MC. Regarding the 92 tumours with paired IHC and mutation results, 86 showed concordant results and six cases were discordant. Three discordant MBT cases showed aberrant expression but were TP53 wild-type on sequencing. Three cases had normal p53 expression but contained a TP53 mutation. Overall, IHC predicted the TP53 mutation status with high sensitivity (94.1%) and specificity (92.7%). The accuracy of IHC was 93.5% with a positive predictive value of 94.1% and a negative predictive value of 92.7%. When comparing MC cases with wild-type TP53 versus those with TP53 mutation, there were no significant differences concerning disease-free survival, local recurrence-free survival, or metastases-free survival (p>0.05). In the MBT subgroup, there were no events for survival analyses. In conclusion, using an independent large sample set of ovarian mucinous tumours, the results of our study confirm that the suggested refined cut-off of strong nuclear p53 staining in ≥12 consecutive tumour cells reflect high accuracy, sensitivity and specificity for an underlying TP53 mutation but the TP53 mutation status has no prognostic significance in either MC or MBT., (Copyright © 2023 Royal College of Pathologists of Australasia. All rights reserved.)

Endometrial carcinoma, endometrial stromal tumours and mixed malignant mesodermal tumours (MMMT) develop along distinctive molecular genetic pathways. Two distinctive types of endometrial carcinoma are distinguished, type I and type II, which develop along distinctive pathways and show different clinical behaviour and histological features. Type I carcinomas show endometrioid histology, are oestrogen-related and develop from atypical endometrial hyperplasia. The molecular tumorigenesis is comparable to colorectal carcinoma with a step-like progression and an accumulation of genetic alterations. Alterations of PTEN, K-Ras mutations and microsatellite instability are frequent and early events in type I carcinoma, whereas p53 mutations occur during progression to grade 3 carcinoma. Serous and clear cell carcinomas are considered type II carcinomas which are mostly unrelated to oestrogen. p53 mutations occur in almost all serous carcinomas and seem to occur early, leading to massive chromosomal instability and rapid tumour progression. Gene expression profiling has supported this dualistic model of endometrial carcinoma. There is evidence of molecular differences between serous and clear cell carcinomas as well as between endometrioid carcinomas with and without microsatellite instability. A dualistic model of tumorigenesis may be also suggested for endometrial stromal tumours. Endometrial stromal sarcomas (ESS; type I endometrial sarcoma) are oestrogen-related and seem to develop from endometrial stromal nodules (ESN). They are histologically and genetically distinct from undifferentiated endometrial sarcoma (UES) which seem to be mostly unrelated to oestrogen (type II endometrial sarcoma). ESS and ESN share the fusion gene JAZF1/JJAZ1 caused by a t(7;17)(p15;q21) translocation, whereas UES lacks a distinctive molecular alteration so far. In MMMT, which is considered a metaplastic carcinoma, p53 alteration occurs early, before clonal expansion and acquisition of genetic diversity during progression.