Overexpression of Her-2/Neu may be an Indicator of Poor Prognosis in Prostate Cancer

Sadasivan, Raj; Morgan, RJ; Jennings, Scott; Austenfeld, Mark S.; Veldhuizen, Peter J. Van; Stephens, Ronald L.; Noble, Mark J.

doi:10.1016/s0022-5347(17)35413-7

Cited by 114 publications

(51 citation statements)

References 11 publications

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“…27 Sadasivan et al found that 9 of 25 prostate carcinoma samples (36%) showed HER-2/neu overexpression, and such overexpression was correlated with tumor grade, stage, and high S-phase and DNA aneuploidy. 15 However, other investigators have reported contradictory results. Formalin fixed prehormone treatment and posthormone treatment specimens from 47 patients were negative for HER-2/neu overexpression when they were evaluated by immunohistochemistry.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of HER‐2/neu expression in prostatic adenocarcinoma

Sanchez

Sweeney

Mass³

et al. 2002

Cancer

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BACKGROUNDSome evidence suggests a role for HER‐2/neu overexpression in prostate carcinoma progression. Reported rates of HER‐2/neu overexpression in patients with prostate carcinoma vary greatly.METHODSThe authors studied radical prostatectomy specimens from 38 patients who had biochemical failure after undergoing radical prostatectomy for prostate carcinoma. Immunohistochemistry for HER‐2/neu overexpression using the HercepTest kit (Dako Corporation, Carpenteria, CA) was employed. Two different antigen‐retrieval techniques were used: 1) the standard U.S. Food and Drug Administration (FDA)‐approved HercepTest assay and 2) a modified HercepTest, which employed an alkaline citrate buffer, pH 9.0, for antigen retrieval and a 1‐hour primary antibody incubation time. The level of HER‐2/neu expression was evaluated on a scale from 0 (no staining) to 3+ according to the published guidelines. Fluorescent in situ hybridization for gene amplification was performed on all specimens.RESULTSWith the standard technique, only one specimen had 2+ staining, and no specimens had 3+ staining. With the modified technique, 10 specimens (26%) had 2+ staining, and 9 specimens (24%) had 3+ staining. There was a significant association between the level of HER‐2/neu expression shown with the modified technique and tumor stage (P = 0.03) as well as Gleason grade (P = 0.01). None of the specimens had HER‐2/neu gene amplification.CONCLUSIONSThe authors report a simple modification of the HercepTest that resulted in an increased rate of HER‐2/neu expression, which was correlated with poor‐risk pathologic findings. The findings suggest that adenocarcinoma of the prostate should be evaluated for HER‐2/neu expression with a prostate specific immunohistochemical procedure that differs from the FDA‐approved standard procedure. Cancer 2002;95:1650–5. © 2002 American Cancer Society.DOI 10.1002/cncr.10839

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Section: Discussionmentioning

confidence: 99%

Evaluation of HER‐2/neu expression in prostatic adenocarcinoma

Sanchez

Sweeney

Mass³

et al. 2002

Cancer

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“…An overexpression of c-ras, c-myc and c-sis oncogenes has been reported (Fleming et al, 1986;Viola et al, 1986;Buttyan et al, 1987), but ras mutations are rare (Gumerlock et al, 1991;Moul et al, 1992). A role of HER-2/neu is not certain (Kuhn et al, 1993;Sadasivan et al, 1993). Recent evidence suggests that tumoursuppressor genes (TSGs) might be more important for the development of prostate carcinoma (Bookstein, 1994;Isaacs, 1995).…”

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Loss of heterozygosity (LOH), malignancy grade and clonality in microdissected prostate cancer

Hügel

Wernert

1999

Br J Cancer

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SummaryThe aim of the present study was to find out whether increasing malignancy of prostate carcinoma correlates with an overall increase of loss of heterozygosity (LOH), and whether LOH typing of microdissected tumour areas can help to distinguish between multifocal or clonal tumour development. In 47 carcinomas analysed at 25 chromosomal loci, the overall LOH rate was found to be significantly lower in grade 1 areas (2.2%) compared with grade 2 (9.4%) and grade 3 areas (8.3%, P = 0.007). A similar tendency was found for the mean fractional allele loss (FAL, 0.043 for grade 1, 0.2 for grade 2 and 0.23 for grade 3, P = 0.0004). Of 20 tumours (65%) with LOH in several microdissected areas, 13 had identical losses at 1-4 loci within two or three areas, suggesting clonal development of these areas. Markers near RB, DCC, BBC1, TP53 and at D13S325 (13q21-22) showed higher loss rates in grades 2 and 3 (between 25% and 44.4%) compared with grade 1 (0-6.6%). Tumour-suppressor genes (TSGs) near these loci might, thus, be important for tumour progression. TP53 mutations were detected in 27%, but BBC1 mutations in only 7%, of samples with LOH. Evaluation of all 25 loci in every tumour made evident that each prostate cancer has its own pattern of allelic losses.

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“…60 High C-ERB-B2 expression is associated with anti-androgen therapy and may contribute to androgen-independence in PC. 61 Sadasivan et al 62 found that C-ERB-B2 expression correlated with advanced stages and higher Gleason scores. Conversely Kuhn et al 63 in a preliminary study of 53 radical prostatectomy (RP) cases, found that C-ERB-B2 protein expression did not predict serological or clinical recurrence.…”

Section: The C-myc Oncogenementioning

confidence: 99%

Molecular biology of prostate cancer

Karayi

Markham

2004

Prostate Cancer Prostatic Dis

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Development of any cancer reflects a progressive accumulation of alterations in various genes. Oncogenes, tumour suppressor genes, DNA repair genes and metastasis suppressor genes have been investigated in prostate cancer. Here, we review current understanding of the molecular biology of prostate cancer. Detailed understanding of the molecular basis of prostate cancer will provide insights into the aetiology and prognosis of the disease, and suggest avenues for therapeutic intervention in the future.

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Overexpression of Her-2/Neu may be an Indicator of Poor Prognosis in Prostate Cancer

Cited by 114 publications

References 11 publications

Evaluation of HER‐2/neu expression in prostatic adenocarcinoma

Evaluation of HER‐2/neu expression in prostatic adenocarcinoma

Loss of heterozygosity (LOH), malignancy grade and clonality in microdissected prostate cancer

Molecular biology of prostate cancer

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