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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.

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.

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IMP3 signatures in fallopian tube. These tubal sections were derived from high-risk group (a), (b), PSC (c), (e), (f), and low-risk group (d). Panel (b) shows IMP3 signatures (arrow) in the low-mid area and the corresponding H&E staining shows morphologically unremarkable tubal epithelial cells (a). Panel (d) shows sporadic cytoplasmic staining of IMP3 in a non-continuous pattern, which is not qualified as IMP3 signatures. Panel (c) shows multiple foci of IMP3 signatures with some corresponding to IMP3-SCE (single arrow, 10–30 positive cells in a row) and some corresponding to IMP3-SCOUTs (double arrow, ≥30 positive cells), which are magnified into panel (e) and panel (f), respectively.
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Figure 2: IMP3 signatures in fallopian tube. These tubal sections were derived from high-risk group (a), (b), PSC (c), (e), (f), and low-risk group (d). Panel (b) shows IMP3 signatures (arrow) in the low-mid area and the corresponding H&E staining shows morphologically unremarkable tubal epithelial cells (a). Panel (d) shows sporadic cytoplasmic staining of IMP3 in a non-continuous pattern, which is not qualified as IMP3 signatures. Panel (c) shows multiple foci of IMP3 signatures with some corresponding to IMP3-SCE (single arrow, 10–30 positive cells in a row) and some corresponding to IMP3-SCOUTs (double arrow, ≥30 positive cells), which are magnified into panel (e) and panel (f), respectively.

Mentions: IMP3 positive tubal epithelial cells ranged from a couple of sporadic tubal epithelial cells to more than 30 epithelial cells in a row (Figure 2). Based on the positively IMP3-stained epithelial cells in tubal mucosal segment, we correlated them to the SCE and SCOUTs based on morphologic and immunophenotypic features of secretory and ciliated cells and the number of secretory cells in a row. After excluding focal staining without qualification of IMP3 signatures, we identified a total of 473 foci of IMP3 signatures in the 316 studied cases. Among them, the number of IMP3 signatures was present in 25 (average of 0.13), 248 (average of 4.13), and 200 (average of 3.33) foci per group cases in the low-risk, high-risk, and PSC group, respectively. This suggests that the number of IMP3 signatures per case was approximately 32 and 26 fold higher in high-risk and PSC group, correspondingly than those in the low-risk group (p < 0.000). Among the all IMP3 signatures, 388 (82%) corresponded to those morphologically identified SCE, termed as IMP3-SCE, while 85 (18%) represented SCOUTs, termed as IMP3-SCOUTs (p < 0.01). Representative pictures of IMP3 staining correlating to SCE and SCOUTs are presented in Figure 2. There were no single IMP3-SCOUTs present in the low-risk group; all of the 85 IMP3-SCOUTs foci were distributed in high-risk group (39, 46%) and PSC group (46, 54%) (p = 0.09).


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 signatures in fallopian tube. These tubal sections were derived from high-risk group (a), (b), PSC (c), (e), (f), and low-risk group (d). Panel (b) shows IMP3 signatures (arrow) in the low-mid area and the corresponding H&E staining shows morphologically unremarkable tubal epithelial cells (a). Panel (d) shows sporadic cytoplasmic staining of IMP3 in a non-continuous pattern, which is not qualified as IMP3 signatures. Panel (c) shows multiple foci of IMP3 signatures with some corresponding to IMP3-SCE (single arrow, 10–30 positive cells in a row) and some corresponding to IMP3-SCOUTs (double arrow, ≥30 positive cells), which are magnified into panel (e) and panel (f), respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: IMP3 signatures in fallopian tube. These tubal sections were derived from high-risk group (a), (b), PSC (c), (e), (f), and low-risk group (d). Panel (b) shows IMP3 signatures (arrow) in the low-mid area and the corresponding H&E staining shows morphologically unremarkable tubal epithelial cells (a). Panel (d) shows sporadic cytoplasmic staining of IMP3 in a non-continuous pattern, which is not qualified as IMP3 signatures. Panel (c) shows multiple foci of IMP3 signatures with some corresponding to IMP3-SCE (single arrow, 10–30 positive cells in a row) and some corresponding to IMP3-SCOUTs (double arrow, ≥30 positive cells), which are magnified into panel (e) and panel (f), respectively.
Mentions: IMP3 positive tubal epithelial cells ranged from a couple of sporadic tubal epithelial cells to more than 30 epithelial cells in a row (Figure 2). Based on the positively IMP3-stained epithelial cells in tubal mucosal segment, we correlated them to the SCE and SCOUTs based on morphologic and immunophenotypic features of secretory and ciliated cells and the number of secretory cells in a row. After excluding focal staining without qualification of IMP3 signatures, we identified a total of 473 foci of IMP3 signatures in the 316 studied cases. Among them, the number of IMP3 signatures was present in 25 (average of 0.13), 248 (average of 4.13), and 200 (average of 3.33) foci per group cases in the low-risk, high-risk, and PSC group, respectively. This suggests that the number of IMP3 signatures per case was approximately 32 and 26 fold higher in high-risk and PSC group, correspondingly than those in the low-risk group (p < 0.000). Among the all IMP3 signatures, 388 (82%) corresponded to those morphologically identified SCE, termed as IMP3-SCE, while 85 (18%) represented SCOUTs, termed as IMP3-SCOUTs (p < 0.01). Representative pictures of IMP3 staining correlating to SCE and SCOUTs are presented in Figure 2. There were no single IMP3-SCOUTs present in the low-risk group; all of the 85 IMP3-SCOUTs foci were distributed in high-risk group (39, 46%) and PSC group (46, 54%) (p = 0.09).

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