Immunohistochemical expression of JAK2, STAT3, POLH, UBE2T, and REV7 in serous ovarian carcinoma: clinicopathological associations and co-expression patterns.

Serous ovarian carcinoma is biologically heterogeneous, and signaling and DNA damage tolerance/repair pathways may jointly influence tumor behavior. This study aimed to perform an integrated immunohistochemical evaluation of JAK/STAT signaling markers and DNA damage tolerance/repair-related markers and to investigate their clinicopathological associations and co-expression patterns. This retrospective cohort included 70 primary serous ovarian carcinomas (66 high-grade serous carcinomas [HGSCs] and four low-grade serous carcinomas [LGSCs]) treated at the Oncology Center, Mansoura University, Egypt, between 2017 and 2024. Tissue microarrays were constructed from formalin-fixed paraffin-embedded surgical tumor tissue and stained for total JAK2, total STAT3, POLH, UBE2T, and REV7. The JAK2 and STAT3 antibodies were not phospho-specific. Marker-clinicopathological and pairwise biomarker associations were evaluated with Benjamini-Hochberg false discovery rate control. Sensitivity analyses were performed in the HGSC cohort (n = 66) and in documented NACT-treated HGSC cases (n = 38). Associations between NACT response category and biomarker expression were explored among 39 documented NACT recipients. Time-to-event analyses were withdrawn following a chronology audit that identified unresolved inconsistencies in the available dates. Positive expression was observed in 58.6% of cases for JAK2, 51.4% for STAT3, 54.3% for POLH, 67.1% for UBE2T, and 62.9% for REV7. UBE2T and REV7 positivity showed nominal associations with earlier primary tumor stage (raw p = 0.019 and p = 0.021, respectively), but neither survived false discovery rate correction across the 85 biomarker-clinicopathological comparisons (q = 0.822 for both). Nine of 10 binary pairwise biomarker associations remained significant after correction, including JAK2-STAT3 (raw p = 0.009; q = 0.011) and JAK2-POLH (raw p = 0.039; q = 0.043). In the HGSC-restricted analysis, the JAK2-STAT3 association remained significant (binary q = 0.003; intensity-correlation q < 0.001). Among the 39 documented NACT recipients, no biomarker was associated with partial versus minimal response after correction (all q = 1.000). In the 38 documented NACT-treated HGSC cases, selected co-expression patterns remained significant, including binary STAT3-UBE2T, POLH-REV7, and UBE2T-REV7 associations (all q < 0.001).t Integrated immunohistochemical profiling identified several FDR-robust co-expression patterns among the evaluated proteins. However, no full-cohort clinicopathological association remained statistically significant after correction for multiple comparisons. Because phosphorylated JAK2 and STAT3 were not assessed, these findings concern total protein abundance rather than pathway activation. The results are exploratory and require replication in larger, independent cohorts using application-specific, independently validated antibodies and prospectively collected clinical data.