GATA3 Expression in HPV-associated and HPV-independent Vulvar Squamous Cell Carcinomas: Patterns of Expression and Prognostic Significance

Abstract

Substantial diminution or loss of GATA3 expression is reportedly frequent in human papillomavirus–independent (HPVI), p53-mediated vulvar intraepithelial neoplasia. Herein, we study GATA3 expression in vulvar squamous cell carcinoma (VSCC) and assess its clinicopathologic significance. Eighty-six cases of VSCC diagnosed at a single institution were immunohistochemically assessed for their expression of GATA3, as well as any possible relationships with patient outcomes and other clinicopathologic parameters. Given that GATA3 expression pattern in the normal vulvar epidermis is typically strong basal staining with a uniform upward extension until at least the mid epidermal layers, VSCCs were scored using a previously reported tripattern system: pattern 0 (>75% tumor staining), pattern 1 (25% to 75% staining), and pattern 2 (<25% staining). Severe loss of GATA3 expression (pattern 2) was present in both human papillomavirus–associated (HPVA) and HPVI VSCC but was significantly more common in HPVI cases (P<0.001). Among 52 HPVA VSCCs, 16 (30.7%), 15 (28.8%), and 21 (40.3%) cases showed patterns 0, 1, 2 staining whereas among 34 HPVI VSCCs, the respective frequencies were 1 (2.9%), 5 (14.7%), and 28 (82.3%). None of the 30 p53 abnormal VSCCs showed pattern 0 staining (0%). Five (16.6%) and 25 (83.3%) showed patterns 1 and 2 staining, respectively. On univariate analysis, the pattern 2 cohort showed a significantly worse overall survival (OS) and disease-free survival (DFS) than the pattern 0 or 1 cohort (P=0.011 and 0.024, respectively), but this finding was not independent of stage on multivariate analysis (P=0.34; hazard ratio: 1.82; 95% CI: 0.55-6.06). Subgroup analysis of the p53 wild-type cases showed significantly worse OS for pattern 2 than the pattern 0 or 1 cohorts, independent of stage (P=0.04; hazard ratio: 6.5; 95% CI: 1.08-39.8). Subgroup analysis of p53 abnormal cases, however, showed no difference in OS and DFS among the 3-tiered GATA3 cohorts. In summary, loss of GATA3 may be seen in both HPVA and HPVI VSCCs but is significantly more common in HPVI SCCs. Loss or substantial diminution of GATA3 expression (pattern 2) is a negative prognostic factor in vulvar SCCs, but only in the p53 wild-type subset, where its negative prognostic significance appears to be independent of stage.