Adipose tissue: a normal constituent of the uterine cervical stroma.

SUMMARY: Mature adipose tissue present in the uterine cervix is not well documented, and believed to represent heterotopic tissue. The purpose of this study was to determine the frequency and histogenesis of adipose tissue in a series of uterine cervix specimens. A total of 100 consecutive cervical loop electrosurgical excision procedure (LEEP) and cone biopsies from patients of mean age 28 years (range: 15 to 57 yr) were examined. The cervix in 30 hysterectomy specimens was also examined. The presence of cervical stromal and parametrial fat, pathologic diagnosis, number of prior cervical biopsies, and prior pregnancies were documented. In a subset, immunohistochemical stains were performed using S-100, and also CD31, CD34, and D2-40 to exclude dilated lymphatics. Mature fat was identified in 17/100 cone/LEEP cases and 2/30 hysterectomy specimens. Fat was located in deep cervical stroma among large vessels in 15/19 (79%) of these cases, and superficially beneath the mucosa admixed with endocervical glands in 4/19 (21%) cases. Patients with cervical fat in cone/LEEP specimens were of mean age 36 years (range: 21 to 57 yr), of which 65% had a squamous intraepithelial lesion and 35% reactive cervicitis. Those with cervical fat in cone/LEEP tissue had on average 2 prior cervical biopsies/case (range: 0 to 5), compared with 1.7 biopsies/case (range: 0 to 10) in those without identifiable fat. These patients with cervical fat had 1 pregnancy/case, whereas those without had 1.7 pregnancies/case. Mature adipose tissue is a normal stromal constituent of the uterine cervix, which may be identified in up to 15% of excision specimens. The presence of cervical fat seems to be unrelated to patient age, parity, parametrial adipose tissue, inflammation, or prior trauma.

Loss of the eukaryotic initiation factor 3f in melanoma.

Aberrant regulation of the translation initiation is known to contribute to tumorigenesis. eIF3 plays an important role in translation initiation. eIF3f is the p47 subunit of the eIF3 complex whose function in cancer is not clear. Initial studies from our group indicated that eIF3f expression is decreased in melanoma. Overexpression of eIF3f inhibits translation and induces apoptosis in melanoma cells. The eIF3f gene is located at chromosome region 11p15.4. Loss of 11p15.4 is a common event in many tumors including melanoma. In order to investigate the molecular mechanism of the decreased expression of eIF3f in melanoma, we performed loss of heterozygosity (LOH) analysis in 24 melanoma specimens using three microsatellite markers encompassing the eIF3f gene. We showed that the prevalence of LOH ranged from 75% to 92% in melanoma. We also performed eIF3f gene copy number analysis using quantitative real-time PCR to further confirm the specific allelic loss of the eIF3f gene in melanoma. We demonstrated a statistically significant decrease of the eIF3f gene copy number in melanoma compared with normal tissues with a tumor/normal ratio of 0.52. To further elucidate the somatic genetic alterations, we carried out mutation analysis covering the entire coding region and 5'UTR of the eIF3f gene in melanoma tissues and cell lines. Despite some polymorphisms, we did not find any mutations. Furthermore, immunohistochemistry analysis demonstrated that eIF3f protein expression is decreased in melanoma compared to benign nevi. These data provide new insight into the understanding of the molecular pathogenesis of eIF3f during melanoma tumorigenesis.

Loss of the eukaryotic initiation factor 3f in pancreatic cancer.

Aberrant regulation of the translation initiation is known to contribute to tumorigenesis. eIF3 plays an important role in translation initiation. eIF3f is the p47 subunit of the eIF3 complex whose function in cancer is not clear. Initial studies from our group indicated that eIF3f expression is decreased in pancreatic cancer. Overexpression of eIF3f induces apoptosis in pancreatic cancer cells. The eIF3f gene is located at chromosome band region 11p15.4. Loss of 11p15.4 is a common event in many tumors including pancreatic cancer. In order to investigate the molecular mechanism of the decreased expression of eIF3f in pancreatic cancer, we performed loss of heterozygosity (LOH) analysis in 32 pancreatic cancer specimens using three microsatellite markers encompassing the eIF3f gene. We showed that the prevalence of LOH ranged from 71% to 93%. We also performed eIF3f gene copy number analysis using quantitative real time PCR to further confirm the specific allelic loss of eIF3f gene in pancreatic cancer. We demonstrated a statistically significant decrease of eIF3f gene copy number in pancreatic tumors compared with normal tissues with a tumor/normal ratio of 0.24. Furthermore, RNA in situ hybridization and tissue microarray immunohistochemistry analysis demonstrated that eIF3f expression is significantly decreased in human pancreatic adenocarcinoma tissues compared to normal pancreatic tissues. These data provides new insight into the understanding of the molecular pathogenesis of eIF3f during pancreatic tumorigenesis.