Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC), microsatellite instability (MSI), and tumor mutation burden (TMB) have been proposed as a predictive biomarker to predict response to immune checkpoint blockade (ICB). We aimed to find the relationship of PD-L1 IHC to TMB and MSI using a comprehensive cancer panel assay (CCPA) with >500 genes in advanced cancer patients. CCPA results from 588 archived tissue samples were analyzed for TMB and MSI. In seven samples, whole exome sequencing confirmed TMB with Pearson’s correlation coefficient of 0.972 and all MSI-high cases were validated by pentaplex PCR. Association of TMB and MSI with their corresponding PD-L1 IHC was analyzed. The median TMB value of 588 cases was 8.25 mutations (mut)/Mb (range 0–426.8) with different distributions among the tumor types, with high proportions of high-TMB (>10mut/Mb) in tumors from melanoma, colorectal, gastric, and biliary tract. The TMB values significantly correlated with PD-L1 expression, and this correlation was prominent in gastric and biliary tract cancers. Moreover, the MSI score, the proportion of unstable MSI sites to total assessed MSI sites, showed a significant correlation with the TMB values and PD-L1 scores. This study demonstrates that PD-L1 expression is significantly associated with TMB and MSI score and this correlation depends on the location of the primary tumor.

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.

Gastric cancer (GC) remains one of the most common deadly malignancies worldwide. Recently, several targeted therapeutics for treating unresectable or metastatic GC have been developed. Comprehensive characterization of the molecular profile and of the tumor immune microenvironment of GC has allowed researchers to explore promising biomarkers for GC treatment and has enabled a new paradigm in precision-targeted immunotherapy. In this article, we review established and promising new biomarkers relevant in GC, with a focus on their clinical implications, diagnostic methods, and the efficacy of targeted agents.

Perivascular epithelioid cell tumor (PEComa) is a very rare mesenchymal tumor with a distinctive morphology and immunophenotype. PEComas usually harbor TSC2 alterations, although TFE3 translocations, which occur in MiT family translocation renal cell carcinoma and alveolar soft part sarcoma, are also possible. We recently experienced a case of PEComa with TFE3 expression arising in the breast. An 18-year-old female patient presented with a right breast mass. Histologically, the tumor consisted of epithelioid cells with alveolar structure and showed a diffuse strong expression of HMB45 and TFE3. TSC2 was preserved. Melan A and smooth muscle actin were negative. To our knowledge, this is the first Korean case of PEComa of the breast that intriguingly presented with TFE3 expression.

Mesonephric adenocarcinoma (MA) of the female genital tract is a rare but distinct entity, exhibiting unique morphological, immunophenotypical, and molecular characteristics. Vaginal MA is hypothesized to arise from the mesonephric remnants located in the lateral vaginal wall. A 52-year-old woman presented with vaginal bleeding. Physical examination revealed a protruding mass in the left vaginal wall. Pelvic magnetic resonance imaging revealed a 2.5-cm mass arising from the left upper vagina and extending posterolaterally to the extravaginal tissue. The punch biopsy was diagnosed as poorly differentiated adenocarcinoma. She received radical surgical resection. Histologically, the tumor displayed various architectural patterns, including compactly aggregated small tubules, solid cellular sheets, endometrioid-like glands and ducts, intraluminal micropapillae, cribriform structure, and small angulated glands accompanied by prominent desmoplastic stroma. The tubules and ducts possessed hyaline-like, densely eosinophilic intraluminal secretions. The tumor extended to the subvaginal soft tissue and had substantial perineural invasion. Immunostaining revealed positivity for the mesonephric markers, including GATA3, TTF1, and PAX2, while showing very focal and weak positivity for estrogen receptor and negativity for progesterone receptor. Additionally, we observed a complete absence of p53 immunoreactivity. Targeted sequencing analysis revealed that the tumor harbored both activating KRAS p.G12D mutation and truncating TP53 p.E286* mutation. A thorough review of the previous literature revealed that 4.5% (3/67) of vaginal/cervical MAs and 0.9% (1/112) of uterine/ovarian mesonephric-like adenocarcinomas harbor TP53 mutations, indicating that this is very uncommon in malignant mesonephric lesions. In summary, we presented a rare case of vaginal MA uniquely harboring pathogenic TP53 mutation, resulting in p53 aberration.