title: Fallopian tube intraluminal tumor spread from noninvasive precursor lesions: a novel metastatic route in early pelvic carcinogenesis.
abstract: Pelvic serous carcinoma is usually advanced stage at diagnosis, indicating that abdominal spread occurs early in carcinogenesis. Recent discovery of a precursor sequence in the fallopian tube, culminating in serous tubal intraepithelial carcinoma (STIC), provides an opportunity to study early disease events. This study aims to explore novel metastatic routes in STICs. A BRCA1 mutation carrier (patient A) who presented with a STIC and tubal intraluminal shedding of tumor cells upon prophylactic bilateral salpingo-oophorectomy (PBSO) instigated scrutiny of an additional 23 women who underwent a PBSO and 40 patients with pelvic serous carcinoma involving the tubes. Complete serial sectioning of tubes and ovaries of patient A did not reveal invasive carcinoma, but subsequent staging surgery showed disseminated abdominal disease. STIC, intraluminal tumor cells, and abdominal metastases displayed an identical immunohistochemical profile (p53/WT1/PAX8/PAX2) and TP53 mutation. In 16 serous carcinoma patients (40%) tubal intraluminal tumor cells were found, compared with none in the PBSO group. This is the first description of a STIC, which plausibly metastasized without the presence of invasion through intraluminal shedding of malignant surface epithelial cells in the tube and subsequently spread throughout the peritoneal cavity. These findings warrant a reconsideration of the malignant potential of STICs and indicate that intraluminal shedding could be a risk factor for early intraperitoneal metastasis. Although rare in the absence of invasive cancer, we show that intraluminal shedding of tumor cells in the fallopian tubes from serous carcinoma cases are common and a likely route of abdominal spread.
authors: Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Jonathan G
authors: JG
authors: Bijron
authors: Cornelis A
authors: CA
authors: Seldenrijk
authors: Ronald P
authors: RP
authors: Zweemer
authors: Joost G
authors: JG
authors: Lange
authors: René H M
authors: RH
authors: Verheijen
authors: Paul J
authors: PJ
authors: van Diest
mesh_terms: D000008:Abdominal Neoplasms / Q000737:chemistry / Q000235:genetics / Q000556:secondary*; D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002278:Carcinoma in Situ / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D004252:DNA Mutational Analysis; D005185:Fallopian Tube Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000737:chemistry / Q000235:genetics / Q000556:secondary* / Q000601:surgery; D010052:Ovariectomy; D051762:PAX2 Transcription Factor / Q000032:analysis; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000032:analysis; D011230:Precancerous Conditions / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D058994:Salpingectomy; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics; D025721:WT1 Proteins / Q000032:analysis
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025721:WT1 Proteins