Serous Tubal Intraepithelial Carcinoma Localizes to the Tubal-peritoneal Junction

Abstract

Recent data suggest that intraepithelial carcinoma of the fallopian tube [serous tubal intraepithelial carcinoma (STIC)] is the precursor of high-grade extrauterine serous carcinoma. A more specific location for the origin of this lesion is suggested by the recently described junction between the fallopian tubal epithelium and the peritoneum [tubal-peritoneal junction (TPJ)]. Fallopian tubes from 202 patients with advanced-stage high-grade extrauterine serous carcinoma or carcinosarcoma were evaluated histologically as were 124 prophylactic salpingo-oophorectomy specimens. These included 54 patients with BRCA or other high-risk mutation or a family history of BRCA mutation and 70 with a personal or family history of breast carcinoma. STIC was found in 81 of 202 patients with serous carcinoma (40.1%). STIC was present in 73 of 141 (52%) cases in which the fimbriae were present and in 62 of 100 (62%) cases in which the TPJ was present (P not significant). In comparison with these groups, when fimbriae and TPJ were absent, STIC was found in 8 of 61 (13%) cases (P<0.0001). None of the prophylactic specimens contained STIC. The mean size of STIC was 1.7 mm. In 32 cases (39.5%), the lesion was flat and in 49 (60.5%), papillary. The mean size of flat STICs was 0.8 mm as compared with 2.3 mm for papillary STICs (P=0.00005). STIC was identified in the same tissue fragment as the junction in 48 cases. The mean distance of STIC to the junction was 1.8 mm. In 11 cases, STIC was flanked by peritoneal mesothelium on one side and tubal epithelium on the opposite side. In 51 patients, the mean distance of invasive carcinoma from the TPJ was 1.8 mm. This distance was 1.9 mm when STIC was present (37 cases) in comparison with 1.5 mm when STIC was absent (14 cases) (P not significant). In 27 of 42 cases (64%), STIC was contiguous with invasive carcinoma. Lamina propria invasion was present in 71% of cases in which STIC was present as compared with 26% of cases in which STIC was absent (P<0.0001). Myosalpingeal invasion was present in 40% of cases in which STIC was present as compared with 26% of cases in which STIC was absent (P not significant). It is concluded that serous tubal intraepithelial carcinoma occurs at and in the immediate vicinity of the TPJ. In combination with the findings that STICs are present in a majority of cases when the TPJ is present, that flat STICs are smaller than papillary STICs, and that lamina propria invasion is more frequent in the presence of STIC, these data support STIC as the precursor of extrauterine high-grade serous carcinoma, they provide important clues to the site of origin of high-grade serous carcinoma (ovarian cancer), and can guide further research.

LEF1 is preferentially expressed in the tubal-peritoneal junctions and is a reliable marker of tubal intraepithelial lesions

“…In such a scenario, it would be more likely to observe random distribution of tumor implants within the tubal fimbria. However, consistent with the recent study by Seidman ( 15 ), we have observed preferential location of STICs at or in the immediate vicinity to the tubal-peritoneal junctions. Furthermore, we have observed similar distribution of STICs in the BRCA1/2 cases, where no overt tumor was observed.…”

“…Recent studies of risk-reducing salpingo-oophorectomies in women with BRCA1/2 germ-line mutations showed that STICs are identified in 2 to 12% of the patients ( 2 , 14 , 26 ). In context of high-grade serous carcinoma the incidence of STIC ranges rather up to 19–60% ( 15 , 27 – 29 ). Our studies have found the frequency of STICs to be 9 % and 45% in the above groups, respectively, thereby confirming the earlier observations.…”

“…A recent study demonstrated that the majority STICs are located in the vicinity of the tubal-peritoneal junction ( 15 ). The tubal-peritoneal junctions connects the columnar epithelium of the fimbriated end of the fallopian tube to the flat mesothelial layer of the peritoneum.…”

Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells

“…The tubal-peritoneal junction connects the columnar epithelium of the fimbriated end of the fallopian tube to the flat mesothelial layer of the peritoneum. Interestingly, most of STICs are located in proximity of the tubal-peritoneal junction [ 191 ]. At the level of the tubal-peritoneal junction putative stem cells were identified, characterized by the expression of LEF1 (Lymphoid Enhancer-Binding Factor 1, a transcription factor that interacts with β-catenin in the nucleus as a component of WNT signaling), thus further supporting the existence of a stem cell niche within the tubal-peritoneal junctions [ 192 ].…”

Identification of candidate genes associated with tubal origin of high‑grade serous ovarian cancer

“…Subsequently, Callahan et al ( 17 ) reported that 7 consecutive cancer cases, from 123 cases of BRCA-positive women undergoing surgery for ovarian cancer risk reduction, originated in the fimbrial or ampullary region of the tube, 6 of which had an early (intraepithelial) component. This was corroborated by evidence supporting the tubal origin of ovarian cancer ( 18 , 19 ). Clonal alterations in TP53 in benign tubal epithelium, which are referred to as p53 signatures, and generic secretory cell outgrowth (SCOUT) in the FTE associated with altered PAX2 expression has established a foundation for a serous cancer precursor in the fimbria ( 10 ).…”