Deciphering the stromal molecular landscape: the correlation between p16 and α-SMA in epithelial ovarian cancer.

Introduction: The tumor microenvironment (TME) plays an essential role in promoting cancer initiation, progression and metastasis. Cancer-associated fibroblasts (CAFs) are a major constituent of the TME, but universal CAFs' markers have not yet been identified. We selected several new biomarkers [p16 and α-smooth muscle actin (α-SMA)] to investigate the molecular landscape in epithelial ovarian cancer (EOC), given to the unique TME of this malignancy.

Methods: In total, 64 patients with a diagnosis of EOC who underwent primary debulking surgery (PDS) at the Department of Gynecology and Obstetrics of the University of Pisa were enrolled between January 2019 and June 2021. The stromal expression of α-SMA and p16 was investigated by using immunohistochemistry, and the correlations between p16 and α-SMA immunoreactivity and BRCA mutational status were analyzed.

Results: Positive p16 stromal expression was found in 6 out of 38 (15,78%) patients with wild-type BRCA and in only 1 of the 22 (4,50%) patients with mutated BRCA. Conversely, positive α-SMA expression was detected in 34 of 38 patients with wild-type BRCA (89,47%) and in 21 of 22 patients (95,45%) with mutated BRCA. There was a significant difference (r = -0,32) between the negative stromal p16 expression and the positive stromal expression of α-SMA.

Conclusion: This study suggests a new correlation between stromal expression of p16 and α-SMA and BRCA mutational status in EOC. Further investigations are strongly warranted to improve the understanding of the landscape of this malignancy.