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Notes: Aim : To test whether α-methylacyl-CoA racemase (AMACR) is a sensitive and specific marker of prostate cancer.Methods and results : The expression levels of AMACR mRNA were measured by real-time polymerase chain reaction. A total of 807 prostatic specimens were further examined by immunohistochemistry specific for AMACR. Quantitative immunostaining analyses were carried out by using the ChromaVision Automated Cellular Imaging System and the Ariol SL-50 Imaging System, respectively. AMACR mRNA levels measured in prostatic adenocarcinoma were 55 times higher than those in benign prostate tissue. Of 454 cases of prostatic adenocarcinoma, 441 were positive for AMACR, while 254 of 277 cases of benign prostate were negative for AMACR. The sensitivity and specificity of AMACR immunodetection of prostatic adenocarcinomas were 97% and 92%, respectively. Both positive and negative predictive values were 95%. By automatic imaging analyses, the AMACR immunostaining intensity and percentage in prostatic adenocarcinomas were also significantly higher than those in benign prostatic tissue (105.9 versus 16.1 for intensity, 45.7% versus 0.02% and 35.03% versus 4.64% for percentage, respectively).Conclusions : We have demonstrated the promising features of AMACR as a biomarker for prostate cancer in this large series and the potential to develop automated quantitative diagnostic tests.

Notes: Aims:  In the female genital tract CD10 has been used to assist in the evaluation of mesenchymal tumours of the uterus and in determining whether endometrial stroma is present. CD10 positivity has also been shown in cervical mesonephric remnants and this antibody has been suggested as a useful immunohistochemical marker of mesonephric lesions in the female genital tract. Calretinin has also been shown to be positive in mesonephric lesions. In this study the specificity of these two antibodies in evaluating cervical and uterine glandular lesions and the value of CD10 in determining whether stroma is endometriotic or not were investigated.Methods and results:  Cases of cervical tubo-endometrial metaplasia (TEM) (n = 11), microglandular hyperplasia (MGH) (n = 10), endometriosis (n = 8), mesonephric remnants/hyperplasia (n = 12), endocervical adenocarcinoma, usual type (n = 15), mucinous variant of minimal deviation adenocarcinoma (MDA) (n = 7) and mesonephric adenocarcinoma (n = 3) were stained with antibodies against CD10 and calretinin. Nine cases of endometrial adenocarcinoma of endometrioid type were also stained. In all the cervical cases normal endocervical glands were negative with both antibodies except for one case with strong positive luminal staining with CD10. All cases of TEM, MGH and endometriosis were negative with CD10 and calretinin except for focal staining with CD10 in one case each of MGH (cytoplasmic staining) and endometriosis (luminal staining). Most usual endocervical adenocarcinomas were negative with both antibodies, although one exhibited focal cytoplasmic staining with calretinin and five exhibited limited luminal positivity with CD10. All MDAs were negative with both antibodies. Ten of 12 mesonephric remnants/hyperplasia showed luminal positivity with CD10 and one exhibited cytoplasmic and nuclear staining with calretinin. Two of three mesonephric adenocarcinomas showed luminal positivity with CD10 and nuclear and cytoplasmic positivity with calretinin. Seven of nine endometrial adenocarcinomas were positive with CD10 (four cytoplasmic, two membranous and cytoplasmic, one luminal and cytoplasmic) and three with calretinin (two cytoplasmic, one nuclear and cytoplasmic). Positive staining of endometriotic stroma with CD10 was present in all endometriosis cases but normal cervical stroma was also strongly positive, especially around glands. Endometriotic stroma and cervical stroma were negative with calretinin.Conclusions:  We conclude that most endocervical glandular lesions, including mesonephric remnants/ hyperplasia, are negative with calretinin. However, the focal nuclear and cytoplasmic positivity with calretinin in two of three mesonephric adenocarcinomas suggests that this may be a useful indicator of a mesonephric origin of a cervical adenocarcinoma. Most mesonephric remnants/hyperplasias exhibit luminal positivity with CD10, although this is not invariable and staining is usually focal. Positive luminal staining of a benign endocervical glandular lesion with CD10 may help confirm mesonephric remnants. Although positive staining with CD10 was found in two of three mesonephric adenocarcinomas, the observed immunoreactivity of several conventional cervical adenocarcinomas limits the diagnostic value of CD10 in confirming a mesonephric origin for an adenocarcinoma. Since all cervical MDAs were negative with CD10, positivity with this antibody may be of value in distinguishing mesonephric hyperplasia from MDA, although this distinction rarely necessitates immunohistochemistry. Most endometrial adenocarcinomas of endometrioid type stain with CD10 and thus positivity with this antibody is not specific for a mesonephric origin of an endometrial adenocarcinoma. Positivity of normal cervical stroma limits the value of CD10 staining in confirming a diagnosis of cervical endometriosis.

Notes: Adenocarcinoma of the uterine cervix and its variants account for a much greater number of cases in routine practice of histopathology than they did several decades ago. The varied morphology of these tumours results in diverse problems in differential diagnosis. The overall area of glandular pathology of the cervix, of which invasive adenocarcinoma is only one subset, is further complicated by the fact that there are many benign glandular proliferations of the cervix that can potentially be misinterpreted as adenocarcinoma. In this review the histopathology of endocervical adenocarcinoma and its variants is presented with the emphasis on evaluation of routinely stained sections, still the bedrock of routine practice, relatively little aid being provided by immunohistochemistry or other new techniques, contrary to what is sometimes implied in the literature. Description of the appearance of each subtype of adenocarcinoma or variant thereof is followed by a section on their differential diagnosis. Eighty percent of endocervical carcinomas are of the so-called usual type being characterized by cells with eosinophilic cytoplasm and generally brisk mitotic activity. It is sometimes stated that endocervical adenocarcinomas are mucinous but the usual form just noted often has little or no mucin. Pure or almost pure mucinous adenocarcinoma do occur, however, and have an important subtype, the so-called adenoma malignum (minimal deviation adenocarcinoma). Although treacherous because of its bland cytological features and sometimes deceptive pattern, a cone biopsy or hysterectomy specimen showing this neoplasm typically has easily recognizable features that indicate the presence of an infiltrative adenocarcinoma. An important variant of usual endocervical adenocarcinoma is the well differentiated villoglandular papillary adenocarcinoma, a designation that should be reserved for tumours with grade 1 cytologic features as usual endocervical adenocarcinoma, which is typically grade 2, may have papillae. In our opinion all other variants of pure adenocarcinoma, including endometrioid, are rare and include in addition to the latter clear cell, serous and mesonephric neoplasms. Tumours witha glandular and nonglandular component are also reviewed: adenosquamous carcinoma, glassy cell carcinoma, adenoid basal carcinoma, ‘adenoid cystic’ carcinoma and adenocarcinoma admixed with a neuroendocrine tumour.