Immunohistochemical Expression Status of p53, CD44v9, and Ki-67 in a Series of Fallopian Tube Lesions of High-grade Serous Carcinoma.

Abstract

Pelvic high-grade serous carcinoma (HGSC) has been postulated to arise via a stepwise accumulation of (epi)genetic alterations from normal epithelium to secretory cell outgrowth (SCOUT), p53 signature, and serous tubal intraepithelial carcinoma (STIC) to invasive HGSC. The aim of this study is to investigate alterations in p53 and CD44v9 expression and the status of Ki-67 labeling index in a series of fallopian tube lesions of HGSC patients. A total of 45 specimens were analyzed in 16 patients with HGSC, and their lesions were categorized as follows: morphologically normal fallopian tube epithelium (FTE, n=6 samples), SCOUT (n=5), p53 signature (n=4), dormant STIC (n=8), active STIC (n=6), and HGSC (n=16). Morphologic features and immunohistochemical expression patterns of the p53 protein, CD44v9 protein, and Ki-67 antigen were blindly evaluated by 2 pathologists. Increased nuclear p53 protein accumulation was observed in p53 signature, dormant STIC, active STIC and HGSC compared with normal FTE and SCOUT (P<0.001). Immunohistochemistry scores of CD44v9 protein expression were significantly higher in normal FTE, SCOUT, and p53 signature than in dormant STIC, active STIC, and HGSC (P<0.001). Both active STIC and HGSC had significantly higher Ki-67 labeling indices than normal FTE, SCOUT, p53 signature and dormant STIC (P<0.001). CD44v9 loss contributes to the stepwise progression of p53 signature to dormant STIC. In conclusion, p53 mutation followed by CD44v9 loss may be involved in the evolution of STIC, which may confer positive clonal selection with a growth and survival advantage.