GATA-binding protein 3 (GATA3) has been identified as a sensitive marker for breast carcinoma but its sensitivity in primary genital extramammary Paget diseases (EMPDs) has not been well studied. Here we investigated immunohistochemical expression of GATA3 in 72 primary genital EMPDs (35 from female, 37 from male; 45 with intraepithelial disease only, 26 with both intraepithelial disease and invasive adenocarcinoma including 14 also metastasis, 1 with metastatic adenocarcinoma only for study). We also compared GATA3 to gross cystic disease fluid protein 15 (GCDFP15) for their sensitivity. Positive GATA3 staining was seen in all 71 (100%) intraepithelial diseases, 25/26 (96%; female 10/10, male 15/16) invasive adenocarcinomas and 14/15 (93%; female 3/3, male 11/12) metastatic adenocarcinomas, respectively. Positive GCDFP15 staining was seen in 46/71 (65%; female 28/34 or 82%, male 18/37 or 49%) intraepithelial diseases, 20/26 (77%; female 9/10, male 11/16) invasive adenocarcinomas, and 12/15 (80%; female 2/3, male 10/12) metastatic adenocarcinomas, respectively (GATA3 versus GCDFP15: p < 0.01 for both intraepithelial disease and invasive adenocarcinoma, p = 0.28 for metastatic adenocarcinoma). In positive-stained cases, GATA3 stained more tumor cells than GCDFP15 (79% versus 25% for intraepithelial disease, 71% vs 34% for invasive adenocarcinoma, 73% vs 50% for metastatic adenocarcinoma, p < 0.01 for all 3 components). Our findings indicate that GATA3 is a very sensitive marker for primary genital EMPDs and is more sensitive than GCDFP15.

Background: Perineural invasion (PNI) is associated with aggressive tumor behavior in several malignancies, but its independent prognostic value in early-stage cervical cancer remains uncertain. We evaluated the clinical significance of PNI and explored molecular and immune features associated with PNI. Methods: We retrospectively analyzed 499 patients with FIGO 2009 stage IB–IIA cervical cancer treated with radical hysterectomy and pelvic lymphadenectomy. Associations between PNI, clinicopathological variables, recurrence-free survival, and overall survival were assessed using Kaplan–Meier methods and Cox regression. An independent cohort of 286 cervical cancers from The Cancer Genome Atlas (TCGA) was analyzed to characterize PNI-associated transcriptomic patterns, pathway enrichment, immune cell composition, and microRNA profiles. Results: PNI was identified in 11.6% of cases and was associated with larger tumor size, deep stromal invasion, and lymphovascular space invasion. PNI was not an independent prognostic factor in the overall cohort; however, it was associated with increased recurrence risk in the subgroup without high-risk factors and not meeting Sedlis criteria, with a modest improvement in 5-year recurrence discrimination when incorporated into Sedlis-based models. In TCGA, PNI was associated with differential gene expression and enrichment of oncogenic and immune-related pathways, an increased estimated abundance of resting mast cells, and six differentially expressed microRNAs. Conclusions: In early-stage cervical cancer, PNI is strongly correlated with established adverse pathological features and shows a subgroup-specific association with recurrence in an otherwise low-risk postoperative population. The multi-omics findings are exploratory and support biological hypotheses regarding tumor–nerve–immune interactions; external validation is needed before PNI can be used to guide postoperative management.