Background: Endocervical adenocarcinomas (ECAs) and endometrial adenocarcinomas (EMAs) are malignancies that affect uterus; however, their biological behaviors are quite different. This distinction has clinical significance, because the appropriate therapy may depend on the site of tumor origin. The purpose of this study is to evaluate 3 different scoring mechanisms of p16 INK4a immunohistochemical (IHC) staining in distinguishing between primary ECAs and EMAs.

This month we revisit the problem of distinguishing endocervical from endometrial adenocarcinomas, a topic that was previously addressed in the January 2002 issue of "Focus on Immunohistochemistry". Most surgical pathologists know very well that there is substantial morphologic overlap between these entities, but differences in therapeutic approaches necessitate attempts to distinguish these 2 tumors.In the January 2002 issue of the International Journal of Gynecological Pathology, two papers addressed this problem. Castrillon et al (1) studied 30 endometrial adenocarcinomas and 29 endocervical adenocarcinomas, and included tumors with overlapping morphologic features. CEA was more common in endocervical adenocarcinomas (62%), than in endometrial adenocarcinomas (27%). The authors also noted that CEA appeared to be particularly useful for tumors that had endometrioid morphology, since only 14% of the endometrial endometrioid adenocarcinomas were CEA positive, in contrast to 67% of the endocervical adenocarcinomas with endometrioid morphology. 97% of the endometrial adenocarcinomas were vimentin positive, in contrast to only 7% of the endocervical adenocarcinomas. McCluggage et al (2) evaluated 30 endometrial adenocarcinomas and 26 endocervical adenocarcinomas. In their study, 93% of endometrial adenocarcinomas were strongly estrogen receptor (ER) positive, whereas focal weak ER positivity was noted in 38% of endocervical adenocarcinomas. Vimentin was diffusely positive in 97% of the endometrial adenocarcinomas, but in only 8% of the endocervical adenocarcinomas. Prior studies have reported ER in 70% of endometrial adenocarcinomas, in contrast to 10-20% of endocervical adenocarcinomas, vimentin reactivity in 50-81% of endometrial adenocarcinomas vs. <13% of endocervical adenocarcinomas, and CEA in 65-95% of endocervical adenocarcinomas. Staebler et al (4) studied 24 endometrial and 24 endocervical carcinomas, and found that only 1 of 24 (4.2%) endocervical carcinomas expressed both ER and PR. In contrast, 18 of 24 (75%) of endometrial carcinomas expressed ER, and 23 of 24 (95.8%) expressed PR. HPV in situ hybridization on formalinfixed paraffin-embedded sections was also performed, which found HPV DNA in 16 of the 24 (66.7%) endocervical carcinomas, but in none of the 24 endometrial carcinomas. In light of the association of immunostaining of p16 (INK4a) with high-risk HPV infection, one might surmise that immunostains for p16 (INK4a) might also be of use in the differential diagnosis of endometrial adenocarcinoma vs. endocervical adenocarcinoma. Although immunohistochemical expression of p16 (INK4a) has been described in both of these tumors, in a study of 24 unequivocal endometrial adenocarcinomas and 18 unequivocal endocervical adenocarcinomas, reported at the recent 2003 USCAP meeting that the pattern of p16 (INK4a) expression allowed distinction of the two tumors. All endocervical adenocarcinomas showed strong and diffuse p16 (INK4a) immunostaining, with a mean of 94% of tumor cells reacting (range 90-100%...

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Background: A novel human nuclear receptor interaction protein (NRIP) has recently been discovered by Chen SL et al, which may play a role in enhancing the transcriptional activity of steroid nuclear receptors in prostate (LNCaP) and cervical (C33A) cancer cell lines. However, knowledge about the biological functions and clinical implications of NRIP, is still incomplete. Our aim was to determine the distribution of NRIP expression and to delineate the cell types that express NRIP in various malignant tumors and healthy non-pathological tissues. This information will significantly affect the exploration of its physiological roles in healthy and tumor cells.

According to the data of p16(INK4a) expression in this TMA study, Method N is favorable and efficient in distinguishing between ECAs and EMAs, while Method C is not.

HER2 protein overexpression correlated significantly with HER2 gene amplification in EOC (P = 0.027). It is surprising that all 4 cases of mucinous EOC showed HER2 gene amplification confirmed by FISH testing. However, we suppose that increasing the number of cases would possibly modify the results. This study also showed that both HER2 gene amplification and somatic mutations are not mutually exclusive in mucinous EOC. Further studies are warranted to investigate the potential role of anti-HER2 therapy.

To date, no study associated the genetic polymorphisms of high-mobility group box 1 protein (HMGB1) with the development of uterine cervical cancer. We therefore conducted this study to investigate the associations of HMGB1 single-nucleotide polymorphisms (SNPs) with cervical carcinogenesis and clinicopathological characteristics of cancer patients. Five hundred two women, including 112 with invasive cancer, 85 with precancerous lesions of the uterine cervix, and 305 normal controls, were consecutively enrolled into this study. Analysis of HMGB1 SNPs was done by real-time polymerase chain reaction and genotyping. Our results found that the risk of susceptibility to cervical invasive cancer was 1.85 (95 % CI 1.12-3.04; p = 0.016) in women with TC and 1.99 (95 % CI 1.24-3.23; p = 0.005) in women with TC/CC after adjusting for age, using TT as a comparison reference in HMGB1 SNP rs1412125. In rs2249825, the increased risk was also seen for the development of cervical invasive cancer in women with CG [adjusted odds ratio (AOR) 2.04, 95 % CI 1.22-3.40; p = 0.006] or CG/GG (AOR 2.02, 95 % CI 1.22-3.32; p = 0.006) using CC as a comparison reference. An additional integrated in silico analysis confirmed that rs2249825 creates a binding site for v-Myb, which may affect HMGB1 expression. In conclusion, Taiwanese women with TC or TC/CC in HMGB1 SNP rs1412125 as well as CG or CG/GG in rs2249825 were susceptible to the development of cervical invasive cancer.

According to our data, when there is histomorphological and clinical doubt as to the primary site of origin, we recommend that the conventional 4-marker (ER/PR/Vim/CEA) panel is appropriate. Ancillary p16(INK4a)-marker testing does not add value to the 4-marker panel in distinguishing between primary ECA and EMA.