Serous tubal intraepithelial carcinoma: its potential role in primary peritoneal serous carcinoma and serous cancer prevention

Abstract

Purpose: A diagnosis of primary peritoneal serous carcinoma (PPSC) requires exclusion of a source in other reproductive organs. Serous tubal intraepithelial carcinoma (STIC; stage 0) has been described in asymptomatic women with BRCA mutations and linked to a serous cancer precursor in the fimbria. This study examined the frequency of STIC in PPSC and its clinical outcome in BRCA-positive women.

Patients and methods: Presence or absence of STIC was recorded in consecutive cases meeting the 2001 WHO criteria for PPSC, including 26 patients with nonuniform sampling of the fallopian tubes (group 1) and 19 patients with complete tubal examination (group 2; sectioning and extensively examining the fimbriated end, or SEE-FIM protocol). In selected cases, STIC or its putative precursor and the peritoneal tumor were analyzed for p53 mutations (exons 1 to 11). Outcome of STIC was ascertained by literature review.

Result: Thirteen (50%) of 26 PPSCs in group 1 involved the endosalpinx, with nine STICs (35%). Fifteen (79%) of 19 cases in group 2 contained endosalpingeal involvement, with nine STICs (47%). STIC was typically fimbrial and unifocal, with variable invasion of the tubal wall. In five of five cases, the peritoneal and tubal lesion shared an identical p53 mutation. Of 10 reported STICs in BRCA-positive women, all patients were without disease on follow-up.

Conclusion: The fimbria is the source of nearly one half of PPSCs, suggesting serous malignancy originates in the tubal mucosa but grows preferentially at a remote peritoneal site. The generally low risk of recurrence in stage 0 (STIC) disease further underscores STIC as a possible target for early serous cancer detection and prevention.

Fig 1.

Sections of fallopian tube (FT) and omental or peritoneal tumors corresponding to areas from which DNA was obtained by laser capture microdissection and subsequently analyzed in duplicate for mutations in exons 1 to 11 of p53 (Table 2). Numbers and locations correspond to cases summarized in Table 2. Cases (C) 1 through C4 contain serous tubal intraepithelial carcinoma based on morphologic criteria, with variable proliferative (MIB-1) index, and are strongly p53-positive in C2 through C4. In C5, benign-appearing p53-positive epithelium (p53 signature, arrows) is adjacent to cancer (large arrowheads), both containing identical p53 mutations (Table 2). Insets in images of the peritoneal tumors in C4 and C5 illustrate strong p53 immunostaining.