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IMP3 signatures of fallopian tube: a risk for pelvic serous cancers.

Wang Y, Wang Y, Li D, Li L, Zhang W, Yao G, Jiang Z, Zheng W - J Hematol Oncol (2014)

Bottom Line: 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.

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ABSTRACT

Background: Recent 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.

Methods: Fallopian 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.

Results: The 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).

Conclusions: The 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.

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IMP3 overexpression in tubal serous tubal intraepithelial carcinoma and invasive serous carcinoma. IMP3 signatures (single arrow, right) shows morphologically bland cells (single arrow, left), which exists in anatomic continuity with tubal serous intraepithelial carcinoma (double arrows). The IMP3 is also diffusely positive in the invasive component of the serous carcinoma (triple arrows), which is located adjacent to the tubal fimbria in a case with PSC.
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Figure 3: IMP3 overexpression in tubal serous tubal intraepithelial carcinoma and invasive serous carcinoma. IMP3 signatures (single arrow, right) shows morphologically bland cells (single arrow, left), which exists in anatomic continuity with tubal serous intraepithelial carcinoma (double arrows). The IMP3 is also diffusely positive in the invasive component of the serous carcinoma (triple arrows), which is located adjacent to the tubal fimbria in a case with PSC.

Mentions: As previously defined, IMP3 signatures contain 10 or more secretory cells in a continuous fashion. IMP3 staining is most frequently observed in secretory cells since the majority of IMP3 signatures tubal segments showed homogeneous staining of a linear contiguous population of PAX8-positive cells (secretory cell marker) lacking the distinctive tubulin (ciliated cell marker) expression (data not shown). Considering the overall number of STIC is much less than IMP3 signatures, we calculated the frequency of positive cases regardless of the number of foci of lesions found in a single case. Overall, the frequency of IMP3-SCE (82%) was more prevalent than IMP3-SCOUTs (18%) in both high-risk and PSC groups. The absolute frequency of STIC in tubal fimbria in the three groups was 0% (0/196), 15% (9/60), and 32% (19/60). The STIC data are comparable to previous findings [[32],[33]]. Among the 9 STIC cases in high-risk group, strong cytoplasmic IMP3 staining (appearing in more than 50% of the neoplastic cells) was found in 5 (55%) cases; similarly, among the 19 STIC cases in PSC group, 11 (58%) were found with strong IMP3 staining. Furthermore, the positive IMP3 expression was found in 38 (63%) of 60 PSC cases. Interestingly, all 11 STIC cases in PSC group with positive IMP3 were also positive for IMP3 in the corresponding invasive cancer area; yet IMP3 signatures in these STIC cases were mainly located in the areas mostly adjacent to the areas of STIC. Representative pictures of IMP3 signatures and IMP3 overexpression in STIC as well as in PSC are illustrated in Figure 3.


IMP3 signatures of fallopian tube: a risk for pelvic serous cancers.

Wang Y, Wang Y, Li D, Li L, Zhang W, Yao G, Jiang Z, Zheng W - J Hematol Oncol (2014)

IMP3 overexpression in tubal serous tubal intraepithelial carcinoma and invasive serous carcinoma. IMP3 signatures (single arrow, right) shows morphologically bland cells (single arrow, left), which exists in anatomic continuity with tubal serous intraepithelial carcinoma (double arrows). The IMP3 is also diffusely positive in the invasive component of the serous carcinoma (triple arrows), which is located adjacent to the tubal fimbria in a case with PSC.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230642&req=5

Figure 3: IMP3 overexpression in tubal serous tubal intraepithelial carcinoma and invasive serous carcinoma. IMP3 signatures (single arrow, right) shows morphologically bland cells (single arrow, left), which exists in anatomic continuity with tubal serous intraepithelial carcinoma (double arrows). The IMP3 is also diffusely positive in the invasive component of the serous carcinoma (triple arrows), which is located adjacent to the tubal fimbria in a case with PSC.
Mentions: As previously defined, IMP3 signatures contain 10 or more secretory cells in a continuous fashion. IMP3 staining is most frequently observed in secretory cells since the majority of IMP3 signatures tubal segments showed homogeneous staining of a linear contiguous population of PAX8-positive cells (secretory cell marker) lacking the distinctive tubulin (ciliated cell marker) expression (data not shown). Considering the overall number of STIC is much less than IMP3 signatures, we calculated the frequency of positive cases regardless of the number of foci of lesions found in a single case. Overall, the frequency of IMP3-SCE (82%) was more prevalent than IMP3-SCOUTs (18%) in both high-risk and PSC groups. The absolute frequency of STIC in tubal fimbria in the three groups was 0% (0/196), 15% (9/60), and 32% (19/60). The STIC data are comparable to previous findings [[32],[33]]. Among the 9 STIC cases in high-risk group, strong cytoplasmic IMP3 staining (appearing in more than 50% of the neoplastic cells) was found in 5 (55%) cases; similarly, among the 19 STIC cases in PSC group, 11 (58%) were found with strong IMP3 staining. Furthermore, the positive IMP3 expression was found in 38 (63%) of 60 PSC cases. Interestingly, all 11 STIC cases in PSC group with positive IMP3 were also positive for IMP3 in the corresponding invasive cancer area; yet IMP3 signatures in these STIC cases were mainly located in the areas mostly adjacent to the areas of STIC. Representative pictures of IMP3 signatures and IMP3 overexpression in STIC as well as in PSC are illustrated in Figure 3.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: Recent 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.

Methods: Fallopian 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.

Results: The 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).

Conclusions: The 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.

Show MeSH
Related in: MedlinePlus