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ABSTRACT: Serous carcinoma is the prototype of type 2 uterine carcinoma. In many cases, establishing a diagnosis is straightforward, but problems can arise in that papillary variants of endometrioid carcinoma may be mistaken for serous carcinoma, and glandular variants of serous carcinoma may be misdiagnosed as endometrioid carcinoma. Markers such as p53, oestrogen receptor and p16 may be of use in problematic cases, but there is overlap and these may not therefore be of value in an individual case. It has been shown recently that high-mobility group AT-hook 2 (HMGA2) is expressed by most ovarian serous carcinomas, and our aim was to ascertain whether it is also expressed in uterine serous carcinoma and of value in its distinction from endometrioid carcinoma.
Whole tissue sections of uterine serous (n = 33) and endometrioid (n = 38) carcinoma were immunostained using HMGA2 antibody. As many of the diagnostic problems relate to the distinction between serous carcinoma and grade 3 endometrioid carcinoma, tissue microarrays (TMAs) containing uterine serous (n = 71) and uterine grade 3 endometrioid (n = 68) carcinomas were also stained. Staining was classified as negative (totally negative or occasional nuclei positive), 1+ (<10% of nuclei positive), 2+ (10-49% of nuclei positive), 3+ (50-74% of nuclei positive), or 4+ (≥75% of nuclei positive). On the whole tissue sections, positive staining was also classified as weak, moderate, or strong, and an immunohistochemical composite score, taking into account both extent and intensity of staining, was calculated. On whole tissue sections, there was a statistically significant difference between HMGA2 staining in serous and endometrioid carcinomas with regard to both extent and composite score, with higher expression in serous carcinomas (P < 0.0001). Thirty of 33 (91%) serous carcinomas were positive, usually with diffuse (3+ or 4+) staining. All five cases of serous endometrial intraepithelial carcinoma (EIC) (the postulated precursor of uterine serous carcinoma) were positive, as were 14 of 38 (37%) endometrioid carcinomas, usually with 1+ or 2+ staining. There was a statistically significant difference in HMGA2 staining in the TMAs between the serous and grade 3 endometrioid carcinomas, with higher expression in the former (P < 0.0001).
Immunoreactivity for HMGA2 is diffusely positive in whole tissue sections in most uterine serous carcinomas and negative in most endometrioid carcinomas, although, as with other markers, there is overlap in individual cases. In conjunction with other markers, HMGA2 may be of value in problematic uterine carcinomas where the differential diagnosis includes serous and endometrioid carcinoma. As HMGA2 is expressed in serous EIC, this suggests that it may be implicated in the early development of uterine serous carcinoma.
Histopathology 03/2012; 60(4):547-53. · 3.08 Impact Factor
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ABSTRACT: So-called ectopic prostatic tissue in the cervix and vaginal tubulosquamous polyps are rare morphologically similar lesions that may show positive immunohistochemical staining with prostatic markers. It has been suggested that they are related to paraurethral Skene's glands that are the female equivalent of prostatic glands in the male. We report a large series of lesions in women aged 23 to 81 years, found within the cervix (n=24), vagina (n=10), and vulva (n=2), which we believe to be a part of a spectrum of lesions derived from Skene's glands, either eutopic or more commonly misplaced during embryonic development. In all cervical cases, the lesion was predominantly situated in the ectocervix and was an incidental finding in specimens procured for a variety of reasons. In the vagina, the lesions usually presented themselves as polyps or cysts, although occasionally they were an incidental finding. The 2 vulval cases were incidental findings in punch biopsies. The basic morphological features were of epithelial elements of both glandular and squamous type; in some cases, the glandular elements formed a double cell layer. Uncommon findings included the presence of sebaceous glands in 2 cases (1 cervix, 1 vagina), basaloid formations resembling hair follicle structures in 4 (2 cervix, 2 vagina), and a microglandular proliferation resembling nephrogenic adenoma in 1 vaginal case. Prostate-specific antigen was positive in 13 of 26 cases and prostatic acid phosphatase in 16 of 26 tested. Six cases were negative with both markers. We propose that these benign lesions in the cervix, vagina, and vulva are derived from eutopic or misplaced Skene's glands.
International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 11/2011; 30(6):605-12. · 2.07 Impact Factor
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ABSTRACT: Numerous studies have investigated p53 immunohistochemistry as a diagnostic, prognostic or predictive marker in various neoplasms. However, the literature is confused and contradictory paying little attention to pivotal aspects of p53 biology nor basic immunohistochemical principles. Here we highlight the effect of varying antibody concentration on p53 immunohistochemical expression. Six uterine endometrioid carcinomas, one uterine serous carcinoma (USC) and a proliferative endometrium were stained with antip53 antibody D07 at varying dilutions. Cases were scored on a scale of 0-6 depending on the percentage of positive nuclei. Greater than 95% of epithelial cells in the USC were positive at all dilutions. The proliferative endometrium exhibited positive staining of >95% of epithelial cells at low dilutions but at high dilutions most epithelial cells were negative. The proportion of positive tumor nuclei in the endometrioid carcinomas varied markedly with antibody concentration. We illustrate that the signal obtained from p53 immunohistochemistry is dependent on antibody concentration. This has diverse implications. First, the p53 labeling index is unreliable without attention to such issues. Second, comparisons between studies are not valid since different antibody concentrations (and other variables) are used. Thirdly, standardization between laboratories is necessary if clinical utility is to be attached to markers including p53. We propose a strategy for determining the optimal p53 antibody concentration.
International Journal of Gynecological Pathology 11/2005; 24(4):307-12. · 1.45 Impact Factor
