Abstract
BackgroundRecent advances suggest fallopian tube as the main cellular source for women’s pelvic serous carcinoma (PSC). In addition to TP53 mutations, many other genetic changes are involved in pelvic serous carcinogenesis. IMP3 is an oncofetal protein which has recently been observed to be overexpressed in benign-looking tubal epithelia. Such findings prompted us to examine the relationship between IMP3 over-expression, patient age and the likelihood of development of PSC.MethodsFallopian tubes from three groups (low-risk, high-risk, and PSC) of patients with matched ages were studied. Age was recorded in 10 years intervals ranging from age 20 to older than 80. The number of IMP3 signatures (defined by 10 or more tubal secretory cells stained positively and continuously in benign appearing tubal mucosa) from both tubal fimbria and ampulla segments was measured. The data was analyzed by standard contingency table and Poisson distribution methods after age adjustment. IMP3 overexpression was also examined in serous tubal intraepithelial carcinoma and PSC.ResultsThe positive IMP3-stained cells are mainly tubal secretory cells. The absolute number of tubal IMP3 signatures increased significantly within each age group. Age remained a significant risk factor for serous neoplasia after age adjustment. IMP3 signatures were more frequent in the patients of both high-risk and PSC groups. The presence of IMP3 signatures in tubal mucosa was significantly associated with tubal or pelvic serous carcinogenesis (p < 0.001).ConclusionsThe findings suggest that tubal secretory cells with IMP3 signatures showing growth advantage could potentially serve as a latent precancer biomarker for tubal or pelvic serous carcinomas in women.
Highlights
Pelvic serous carcinoma (PSC), including serous cancers of the ovary, peritoneum, and fallopian tube, is the most common and lethal type of mullerian malignancy, comprising more than 70% of all malignancies from these considered as a latent precancer associated with clonal alterations of p53 expression [15,16,17]
The incidence of IMP3 signatures increased with age Cells with IMP3 signature represented tubal secretory cells
IMP3 signature increment was independently associated with age, high-risk factors, and the status of pelvic serous carcinoma Noting that the increased number of tubal IMP3 signatures is associated with age and more frequent in highrisk and PSC patients, we explored whether the increased number of IMP3 signatures in high-risk or PSC patients are independent of age
Summary
Pelvic serous carcinoma (PSC), including serous cancers of the ovary, peritoneum, and fallopian tube, is the most common and lethal type of mullerian malignancy, comprising more than 70% of all malignancies from these considered as a latent precancer associated with clonal alterations of p53 expression [15,16,17]. We have re-examined the issue and found secretory cell expansion (SCE), defined as ≥ 10 secretory cells in a row, is a more sensitive biomarker than SCOUTs for pelvic serous carcinogenesis [15]. This was supported by the observation that SCEs were found in a significantly higher frequency in tubal mucosa from patients with high-risk of development of PSC [15]. Such findings prompted us to examine the relationship between IMP3 over-expression, patient age and the likelihood of development of PSC
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