Mismatch repair status in high-grade endometrial carcinomas of endometrioid and non-endometrioid type.

PURPOSE: To evaluate mismatch repair (MMR) status in a series of high-grade endometrial carcinomas and correlate it with several clinicopathological characteristics and with survival. METHODS: One hundred and one patients with high-grade endometrial carcinoma, both of endometrioid and of non-endometrioid type were included in the study. The expression of MLH1, MSH2, MSH6 and PMS2 was evaluated by immunohistochemistry. RESULTS: In our cohort, 41 women had an endometrioid and 60 women a non-endometrioid carcinoma. Endometrioid histotype was statistically more frequent in deficient MMR (dMMR) tumors (73.3%), while non-endometrioid carcinomas in proficient (pMMR) cases (73.8%) (p<0.001). When analyzing the group of endometrioid and non-endometrioid carcinomas separately, only dMMR endometrioid cancers were found to be statistically related to deep myometrial invasion, lymph-node metastases and advanced stage (p=0.035, p=0.011 and p=0.028, respectively). Univariate and multivariate analysis revealed no relation between MMR status and progression-free survival (PFS) or overall survival (OS). Adjuvant treatment was not found to influence the course of the disease. When MMR proteins were studied separately, MLH1/PMS2 loss was related to deep myometrial invasion (p=0.019 and p=0.036, respectively) and MSH6 loss to lymph-node metastases (p=0.04). CONCLUSIONS: In our group of high-grade endometrial carcinomas, MMR deficiency was statistically more frequent in endometrioid than in non-endometrioid cancers. Furthermore, only dMMR endometrioid type grade 3 carcinomas were found to be related with features indicative of aggressive behavior. Considering some unique relation of each MMR protein with distinct clinicopathological features, the assessment of all four proteins is proposed.

The impact of programmed cell death-ligand 1 (PD-L1) and CD8 expression in grade 3 endometrial carcinomas.

BACKGROUND: To evaluate the expression of programmed cell death-ligand 1 (PD-L1) and CD8 in high-grade endometrial carcinomas and relate it to several clinicopathological parameters. METHODS: One hundred and one (101) patients with high-grade endometrial carcinomas who were completely surgically staged were included in this study. PD-L1 and CD8 + expression was evaluated by immunohistochemistry. RESULTS: In our cohort, 47 women (46.5%) had endometrioid carcinomas and 54 patients (53.5%) were diagnosed with non-endometrioid cancers. In endometrioid carcinomas, there was a significantly higher rate of positivity for PD-L1 expression (p = 0.042) and of intraepithelial CD8 + cell counts (p = 0.004) as opposed to non-endometrioid cancers. There were no significant relationships with any of the other clinicopathological features under study. Univariate and multivariate analysis revealed that only high intraepithelial CD8 + counts (p = 0.01) was associated with longer progression-free survival. Tumors positive for PD-L1 and high intraepithelial CD8 expression were mainly of endometrioid histology, whilst PD-L1-positive/CD8 low and PD-L1-negative/CD8 low tumors were mostly non-endometrioid carcinomas (p = 0.01). PD-L1 negative/CD8 high tumors had the longest progression-free survival (p = 0.032). CONCLUSIONS: In grade 3 endometrial carcinomas, both of endometrioid and non-endometrioid type, high intraepithelial CD8 + counts represent an independent favorable prognostic factor and when related to PD-L1-negative tumors, a longer progression-free survival can be predicted. Immunotherapy could probably be considered for PD-L1-positive/CD8 + high tumors, which were mostly of endometrioid histology.

Assessing the landscape of ovarian serous borderline tumors.

AIM: To compare distinct clinicopathological features between atypical proliferative serous tumors and non-invasive low-grade ovarian serous carcinomas. METHODS: Our study group comprised 203 cases of serous borderline tumors sub-classified as atypical proliferative serous tumors or as non-invasive low-grade serous carcinomas. All pathological features related to borderline tumors were re-evaluated by two gynecological pathologists. Data concerning recurrences and survival were retrieved from the medical records of the patients. RESULTS: When comparing atypical proliferative serous tumors to non-invasive low-grade serous carcinomas, the latter were statistically related to advanced stage at diagnosis, bilateral disease, exophytic pattern of growth, microinvasive carcinoma, and the presence of invasive implants. In univariate analysis, recurrences were statistically related to the exophytic pattern of growth, to microinvasion, and to the presence of implants (both invasive and non-invasive). Nevertheless, in multivariate analysis, only microinvasion and the presence of invasive implants were related to recurrence. Women who eventually succumbed to the disease were only those with invasive implants. Their ovarian tumor was either a non-invasive low-grade serous carcinoma or an atypical proliferative serous tumor with 'minimal' micropapillary pattern. Neither lymph node involvement nor endosalpingiosis seemed to influence the course of the disease. CONCLUSIONS: The results of our study underline the increased possibility of non-invasive low-grade serous carcinomas to be related with features indicative of aggressive behavior as opposed to atypical proliferative serous tumors. Nevertheless, irrespective of tumor histology, the presence of invasive implants and microinvasion were the only independent prognostications of recurrence.