To investigate and compare topoisomerase II-alpha expression in benign prostatic hyperplasia (BPH), prostate cancer of varying Gleason scores and hormone-insensitive prostate cancer.The immunohistochemical expression of topoisomerase II-alpha antibody in the above-mentioned diagnostic categories was investigated and compared.Increased expression of topoisomerase II-alpha was seen in the prostate cancers of Gleason scores 7 and 8-10 (p = 0.000) compared with prostate cancers of Gleason score 6 and BPH (p = 0.245). Statistically significant differences were found in the topoisomerase II-alpha gene expression between prostate cancers categorised by Gleason Score. Also, increased expression of topoisomerase II-alpha was seen in the known hormone-resistant prostate carcinomas compared with prostate cancers with no hormone treatment in the subgroup with Gleason scores 8-10, which approached statistical significance (p = 0.081). No statistically significant difference was observed in topoisomerase II-alpha expression between the groups with BPH and prostate carcinoma of Gleason score 6 (p = 0.245).Topoisomerase II-alpha expression was found to increase with the known prognostic marker Gleason score and with hormone insensitivity. Objective evidence is provided for clinical trials with drugs targeting topoisomerase II-alpha to be targeted to patients with prostate cancers of Gleason Score >6 and, in particular, prostate cancers of Gleason Scores 8-10.
O'Hurley G, Perry A S, O'Grady A, Loftus B, Smyth P, O'Leary J J, Sheils O, Fitzpatrick J M, Hewitt S M, Lawler M & Kay E W (2011) Histopathology 59, 1240–1248 The role of secreted frizzled-related protein 2 expression in prostate cancer Aims: Improved prostate cancer (PCa)-specific biomarkers are urgently required to distinguish between indolent and aggressive disease, in order to avoid overtreatment. In this study, we investigated the prostatic tissue expression of secreted frizzled-related protein (SFRP)-2. Methods and results: Following immunohistochemical analysis on PCa tissue microarrays with samples from 216 patients, strong/moderate SFRP-2 expression was observed in epithelial cells of benign prostatic hyperplasia, and negative/weak SFRP-2 expression was observed in the majority of tumour epithelia. However, among Gleason grade 5 carcinomas, 40% showed strong/moderate SFRP-2 expression and 60% showed negative SFRP-2 expression in epithelial cells. Further microscopic evaluation of Gleason grade 5 tumours revealed different morphological patterns, corresponding with differential SFRP-2 expression. The first subgroup (referred to as Type A) appeared to have a morphologically solid growth pattern, whereas the second subgroup (referred to as Type B) appeared to have a more diffuse pattern. Furthermore, 100% (4/4) of Type A patients experienced biochemical recurrence, as compared with 0% (0/6) of Type B patients. Conclusions: These results imply: (i) that there is a loss of SFRP-2 expression from benign to malignant prostate glands; and (ii) differential SFRP-2 expression among two possible subgroups of Gleason grade 5 tumours.
Alpha-methylacyl-CoA racemase (AMACR) is a sensitive and specific immunohistochemical marker of prostatic malignancy, staining 80-100% of prostatic cancers with absent staining in benign glands. However, positive staining in benign conditions as well as low rates of AMACR reactivity in prostatic cancer variants have been described. Preliminary use of AMACR immunohistochemistry in our institution has suggested lower specificity and sensitivity for prostatic cancer than initially proposed. The aim of this study was to establish true rates of AMACR reactivity in prostatic cancer and benign prostatic hyperplasia (BPH).AMACR immunohistochemistry was performed on sections from 57 prostatic cancers and 44 BPH resections. Ninety-one percent of cancers were AMACR+, with diffuse (> 75%) tumour staining in 53% of cases. Thirty-eight percent of tumours showed heterogeneous expression (1-75% tumour staining). This was significantly correlated with increased Gleason score. High-grade prostatic intraepithelial neoplasia (PIN) was AMACR+ in 87% of cancers. Eleven percent of BPH showed moderate or strong staining in benign glands, focally mimicking the malignant staining pattern.This study confirms heterogeneous AMACR expression in prostatic cancer and shows a correlation with Gleason score. Positive staining in BPH is also documented, thus emphasizing the importance of interpreting AMACR immunohistochemistry in the context of other findings in a diagnostic setting.
Subacute cutaneous lupus erythematosus (SCLE) is a recognised variant of lupus erythematosus (LE), which accounts for 10-15% of all cases of cutaneous LE, occurring most commonly in young to middle-aged white women. Diagnosis is based on the detection of anti-Ro/SS-A antibodies in the skin and serum, characteristic clinical and histological cutaneous involvement, and relatively mild systemic involvement. Several unusual variants of SCLE have been reported including erythrodermic SCLE, SCLE with vitiligo-like lesions, acral SCLE and bullous SCLE. Poikoilodermatous SCLE is a recognised but rare variant of SCLE. There are currently only two case reports, comprising five individual cases, in the literature. We present a case of SCLE in which the main clinical findings were an extensive photodistributed poikilodermatous rash and alopecia.
We evaluated the prognostic significance of overexpression of cyclin D1 in 47 patients with surgically resected squamous cell carcinomas of the head and neck. Overexpression of cyclin D1 was detected immunohistochemically using an affinity-purified polyclonal antibody directed against the carboxyl-terminal part of the cyclin D1 protein, applied to formalin-fixed, paraffin-embedded tissue sections. Overexpression of cyclin D1 was found in 30 of 47 head and neck squamous cell carcinoma (HNSCC) cases and was associated with a more rapid and frequent recurrence of disease (P = 0.027). There was a 5-year disease-free interval of 47% for HNSCC patients with a strong overexpression of cyclin D1 and of 80% for cyclin D1-negative HNSCC patients. Overexpression of cyclin D1 was also associated with a shortened overall survival of these patients (P = 0.0095), with a 5-year survival of 60% for the cyclin D1 strongly positive cases and of 83% for cyclin D1-negative cases. Overexpression of cyclin D1 appears to indicate poor prognosis in operable HNSCC.
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