Scoring of p16INK4a immunohistochemistry based on independent nuclear staining alone can sufficiently distinguish between endocervical and endometrial adenocarcinomas in a tissue microarray study

Abstract

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%...

Expression profiles of carcinosarcoma of the uterine corpus—are these similar to carcinoma or sarcoma?

“…Immunohistochemical (IHC) staining was scored according to the German semiquantitative system, in which numbers are assigned based on the percentage of positively staining cells (0 indicates 0%; 1, 1% to 10%; 2, 11% to 50%; 3, 51% to 80%; 4, 81% to 100%) and their intensity (0 indicates no staining; 1, weak staining; 2, moderate staining; and 3, strong staining) (Han et al, 2009). The IHC score was calculated by multiplying the percentage score by the intensity score to yield values ranging from 0 (no expression) to 12 (strongest possible expression).…”

Cell Block Preparation versus Liquid-Based Thin-Layer Cervical Cytology: A Comparative Study Evaluating Human Papillomavirus Testing by Hybrid Capture-2/Cervista, in situ Hybridization and p16 Immunohistochemistry

“…A recent study by del Pino et al [48] highlighted its potential value as a prognostic marker of dysplasia progression and regression in a series of patients with biopsy-proven CIN 1 lesions. Many investigators advocate the use of p16 IHC as an adjunct method in evaluating high-risk HPV presence in cervical lesions [19,20,21,22,23,24,25,26,27,28]. This would ultimately improve diagnostic accuracy leading to better therapeutic decisions.…”

“…p16, an excellent surrogate marker of HPV E7 functional inactivation of retinoblastoma gene protein, is a cyclin-dependent kinase inhibitor and a marker of cell cycle dysregulation [17,19,20]. The diagnostic value of p16 overexpression has been proven in high-risk HPV infections in high-grade squamous intraepithelial lesions (HSIL) and various squamous and endocervical carcinomas [21,22,23,24]. Many investigators advocate the use of p16 IHC as an adjunct method in evaluating high-risk HPV presence in cervical lesions [4,25,26,27,28].…”

Evaluation of different p16 immunostaining methods and the prognostic role of p16/Ki-67 combined expression in non-muscle invasive bladder cancers

“…However, the functional and biological importance of cytoplasmic staining is not yet understood [35]. Some studies on p16 expression take into account only nuclear staining [1,24,36], while others consider both nuclear and cytoplasmic staining [18,19,23].…”

“…Han et al compared endocervical carcinomas and endometrial adenocarcinomas in terms of p16 expression. Use of nuclear staining only as a reference for scoring was claimed to be the most adequate and effective method [35]. Similarly, in a study evaluating p16 expression in ovarian cancer, Kommoss et al took into consideration only nuclear staining in scoring [36].…”