Mesonephric-like Adenocarcinoma of the Uterine Corpus: Comprehensive Immunohistochemical Analyses Using Markers for Mesonephric, Endometrioid and Serous Tumors

Abstract

Mesonephric-like adenocarcinoma (MLA) of the uterine corpus is a rare but distinct malignant tumor of the female genital tract, demonstrating a characteristic morphology and unique immunohistochemical profiles and molecular alterations. We conducted immunohistochemical staining (IHC) to make precise differential diagnoses of uterine MLAs from common histological subtypes of endometrial carcinomas. We collected 25 uterine MLAs and performed IHC for GATA3, TTF1, CD10, ER, PR, p16, p53, and HER2. Seventeen cases (68.0%) showed at least moderate nuclear GATA3 immunoreactivity in ≥25% of tumor cells. Most cases expressed TTF1 (17/21, 81.0%) and CD10 (luminal; 17/21, 81.0%). Heterogeneous TTF1 expression was noted in 12 cases. An inverse pattern of GATA3 and TTF1 staining was observed in eight cases (32.0%). Three cases (12.0%) showed moderate-to-strong ER expression in ≥25% of tumor cells, and two cases (8.0%) showed moderate-to-strong PR expression in ≥5% of tumor cells. These hormone receptor-positive MLAs varied in intensity and proportion of GATA3 staining. None of the 25 cases exhibited either diffuse and strong p16 expression or aberrant p53 expression. Five cases (20.0%) showed equivocal HER2 immunoreactivity (score 2+), but HER2 FISH confirmed that none of them exhibited HER2 gene amplification. In summary, a small subset of uterine MLAs displayed atypical IHC results: focal but strong expression of ER or PR, the complete absence of GATA3 immunoreactivity, the concurrent expression of mesonephric and hormone receptors, and the inverse pattern of GATA3 and TTF1 staining. These unusual immunophenotypes may complicate the differential diagnosis of MLA. Moreover, pathologists should be encouraged to interpret the IHC results cautiously.

Mesonephric-like Adenocarcinoma of the Ovary: Clinicopathological and Molecular Characteristics

“…Our results of consistent GATA3 immunostaining in all cases corroborated the previous data. Regarding hormonal receptors, similar to previous studies, our ovarian MLA cases rarely showed ER and PR expression with weak-to-moderate staining intensity [ 39 , 40 , 41 , 42 ]. Even though it can be confusing to differentiate MLA from EC with the assumption of the low specificity of ER and PR, low-grade EC mimicking MLA would exhibit well-differentiated tubules or ductal structures showing uniform and strong expression for both ER and PR.…”

“…Pors et al [ 9 ] also reported the 5-year PFS of 43 uterine MLA patients as 27.5%. We also recently demonstrated that 64% (16/25) of uterine MLA patients were diagnosed as having stage III–IV tumors, and 18 (72%) patients experienced post-operative recurrences [ 39 ]. Taken together, we prudently assume at least that ovarian MLA might present as a relatively early-stage disease and more favorable prognosis than uterine MLA which is known to exhibit very aggressive clinical behavior and dismal prognosis.…”

Mesonephric Adenocarcinoma of the Vagina Harboring TP53 Mutation

“…Five of the six examined patients showed negative estrogen-receptor expression, and progesterone receptor was absent in all six examined patients. Despite the small number of examined patients, the positive rates of mesonephric markers and hormone receptors was similar to that observed in uterine MLA [ 24 ]. Information on TP53 mutation was available only in our case.…”

Mesonephric-like Adenocarcinoma of the Uterine Corpus: Comprehensive Analyses of Clinicopathological, Molecular, and Prognostic Characteristics With Retrospective Review of 237 Endometrial Carcinoma Cases

“…to distinguish uterine MLA from more commonly encountered histological types of endometrial carcinoma, including endometrial endometrioid carcinoma (EC) (10), serous carcinoma (SC), and carcinosarcoma (CS). A unique immunophenotype of MLA has also been documented in the literature (2,6,13,14). The following expression patterns support the diagnosis of MLA: positive immunoreactivities for mesonephric markers, including GATA-binding protein 3 (GATA3), paired box 2 (PAX2), transcription termination factor 1 (TTF1), and cluster of differentiation 10 (CD10); negative or only focal expression of hormone receptors; non-diffuse p16 positivity; and wild-type p53 immunostaining pattern (1,2,5,6,8,9).…”

“…A unique immunophenotype of MLA has also been documented in the literature (2,6,13,14). The following expression patterns support the diagnosis of MLA: positive immunoreactivities for mesonephric markers, including GATA-binding protein 3 (GATA3), paired box 2 (PAX2), transcription termination factor 1 (TTF1), and cluster of differentiation 10 (CD10); negative or only focal expression of hormone receptors; non-diffuse p16 positivity; and wild-type p53 immunostaining pattern (1,2,5,6,8,9). Molecular studies using targeted next-generation sequencing (NGS) revealed that patients with uterine MLA frequently harbor a pathogenic mutation in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene, as well as alterations in neuroblastoma viral oncogene homolog, AT-rich interaction domain (ARID1A), phosphatidylinositol-4,5bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), βcatenin, patched 2, and tumor protein 53 (TP53) (1,8,9,15).…”