Zaibo Li

Identifying mesonephric‐like adenocarcinoma of the endometrium by combining SOX17 and PAX8 immunohistochemistry

AimsMesonephric‐like adenocarcinoma (MLA) of the endometrium or ovary is a rare but distinct endometrial carcinoma which has a combination of characteristic morphological, immunohistochemical (IHC) and molecular features. SOX17 has been recently identified as a highly sensitive and specific marker for endometrial and ovarian carcinomas. In this study, we aimed to investigate SOX17 expression in MLA together with other IHCs to differentiate MLAs from other endometrial carcinomas.MethodsSeventeen previously diagnosed endometrial/ovarian MLAs were collected, and multiple IHCs were performed. Additionally, we performed SOX17, PAX8 and ER on tissue microarrays (TMAs) composed of 652 endometrial carcinomas from 2012 to 2015 when MLA diagnostic criteria were not established.ResultsAll 17 MLAs showed diffuse strong positive PAX8, negative ER and variable TTF1/GATA3 staining. Notably, all MLAs showed negative (n = 10) or focal weak/moderate (n = 7) staining for SOX17, which is more diffuse and stronger than PAX8 in other endometrial carcinoma subtypes. This finding prompted us to screen TMAs with 652 endometrial carcinomas diagnosed before MLA by an approach of combined SOX17 and PAX8 IHCs, and 14 cases with positive PAX8 but negative/focal weak SOX17 were identified. We further studied the 14 cases by examining morphology and performing additional IHCs (TTF1, GATA3, ER and CD10) and would classify seven (50%) of them as MLAs based on morphological features and positive CD10, TTF1 and/or GATA3 staining.ConclusionOur results suggest that a combination of SOX17 and PAX8 IHCs would aid in diagnosing MLA if the results show strong positive PAX8, but negative SOX17.

SOX17 is a highly sensitive and specific marker for metastatic ovarian and endometrial carcinomas in cytology cell block specimens

AbstractBackgroundSOX17 (SRY‐box transcription factor 17) was recently identified as a highly sensitive and specific marker for ovarian and endometrial carcinomas in surgical specimens. In this study, validation of the utility of SOX17 immunohistochemistry (IHC) in diagnosing metastatic gynecologic carcinomas in cytology specimens was sought.MethodsThe study cohort included 84 cases of metastatic carcinomas that included 29 metastatic gynecologic carcinomas (24 ovarian high‐grade serous carcinomas, two endometrial serous carcinomas, one low‐grade serous carcinoma, one ovarian clear cell carcinoma, and one endometrial endometrioid carcinoma) and 55 cases of metastatic nongynecologic carcinomas (10 clear cell renal cell carcinomas, 10 papillary thyroid carcinomas, 11 gastrointestinal adenocarcinomas, 10 breast carcinomas, 10 lung adenocarcinomas, and four urothelial carcinomas). Cytology specimen types included peritoneal fluid (n = 44), pleural fluid (n = 25), and fine‐needle aspiration (n = 15). SOX17 IHC was performed on the cell block sections. The intensity of staining and percent positivity of the tumor cells were evaluated.ResultsSOX17 was highly expressed in all tested metastatic gynecologic carcinomas with diffuse and strong nuclear expression (29 of 29; 100%). SOX17 was negative in other metastatic nongynecologic carcinomas (54 of 55; 98.18%) except for one papillary thyroid carcinoma that showed low positivity (<10%).ConclusionsSOX17 is a highly sensitive (100%) and specific (98.2%) marker for the differential diagnosis of metastatic gynecologic carcinomas in cytology specimens. Therefore, SOX17 IHC should be included in the workup of differential diagnosis of metastatic gynecologic carcinomas in cytology specimens.

HER2 Gene Protein Assay: A Robust Tool for Evaluating HER2 Status and Intratumoral Heterogeneity in Endometrial Cancers

Abstract Objectives Human epidermal growth factor receptor 2 (HER2) status in endometrial cancer is usually determined by immunohistochemistry and/or in situ hybridization. We employed a novel HER2 gene protein assay (GPA) to simultaneously assesses HER2 gene amplification and protein expression in high-grade endometrial cancers. Methods We performed GPA in 180 endometrial cancers, including 106 serous carcinomas, 34 carcinosarcomas, and 40 mixed epithelial carcinomas. HER2 status was determined using the 2018 HER2 guidelines for breast carcinoma, and HER2 intratumoral heterogeneity (ITH) was examined. Clinicopathologic characteristics were collected and correlated with HER2 status. Results HER2 positivity was noted in 32% of serous carcinomas, significantly higher than in carcinosarcomas (5.9%) and mixed carcinomas (12.5%). HER2 ITH was detected in 32% of serous carcinomas, significantly greater than in carcinosarcomas (8.8%) and mixed carcinomas (10%). Patients with carcinosarcoma had a significantly lower overall survival than patients with serous or mixed epithelial carcinoma, but HER2 status caused no difference in survival in patients with serous carcinoma. Conclusions HER2 GPA can be used to accurately determine HER2 status in endometrial cancers and is a highly valuable tool for identifying HER2 heterogeneity.

Identifying SOX17 as a Sensitive and Specific Marker for Ovarian and Endometrial Carcinomas

Similar to PAX8, SOX17 was recently identified as a master transcription factor of ovarian cancer based on RNA sequencing data. We explored SOX17 utility in diagnosing ovarian tumors and other gynecologic tumors. We systematically evaluated SOX17 expression on tissue microarrays of 398 ovarian tumors of various types, 93 endometrial carcinomas, 80 cervical carcinomas, and 1371 nongynecologic carcinomas, such as those of kidney, thyroid, breast, colon, bladder, liver, bile duct, adrenal gland, pancreas, brain, and lung and malignant melanoma. In addition, we evaluated SOX17 expression in whole tissue sections from 60 gynecologic carcinomas and 10 angiosarcomas. The results demonstrated that SOX17 was highly expressed in most ovarian and endometrial tumors with strong intensity. However, unlike PAX8, it was predominately negative in other tested tumor types, including kidney and thyroid tumors. In particular, SOX17 was highly expressed in the following pathologic subtypes of ovarian tumors: serous carcinoma, clear cell carcinoma, endometrioid carcinoma, and germ cell tumors. SOX17 was mostly negative in mucinous carcinoma and sex cord stromal tumors. In addition, SOX17 was expressed in vascular endothelial cells and was positive in all tested angiosarcomas. In summary, our results demonstrate that SOX17 is a sensitive and specific marker for ovarian nonmucinous carcinomas and endometrial carcinomas. For ovarian germ cell tumors and angiosarcomas, SOX17 demonstrates higher specificity than PAX8, with comparable sensitivity. Furthermore, SOX17 positivity in endothelial cells serves as an internal positive control, making it an excellent marker.

The reporting rates of high‐grade squamous intraepithelial lesions and their human papillomavirus testing and histologic follow‐up results: A comparison between ThinPrep and SurePath preparations

AbstractBackgroundLiquid‐based cytology (LBC) tests SurePath (SP) and ThinPrep (TP) have largely replaced conventional Papanicolaou (Pap) tests for cervical cytology screening due to higher sensitivity. However, comparison between SP and TP test sensitivity and efficacy in detecting squamous abnormalities is lacking. Our study aims to compare high‐grade squamous intraepithelial lesion (HSIL) reporting rates, human papillomavirus (HPV) positivity rates, and histologic outcome between these two LBC methods.Materials and MethodsWe performed a retrospective search of the period between January 2014 and June 2017, when both TP and SP were utilized at our institution, to identify HSIL cases and collect the HPV testing and histologic follow‐up results for those cases.ResultsOne hundred twenty‐five HSILs were identified from the 15 382 TP specimens (0.81%) and 93 HSILs were identified from the 25 105 SP specimens (0.37%), a statistically significant difference (P < .0001). The corresponding HPV positivity rates were 95.6% and 89.7% in TP‐HSILs and SP‐HSILs, respectively, a statistically non‐significant difference. Histologic follow‐up showed HSILs or carcinomas were identified in 78% (49/63) of TP‐HSILs and 79% (45/57) of SP‐HSILs, with no statistically significant difference.ConclusionTP demonstrated a higher HSIL detection rate than SP with no significant difference in follow‐up HPV or histologic results.