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Novel dual-color immunohistochemical methods for detecting ERG-PTEN and ERG-SPINK1 status in prostate carcinoma.

Bhalla R, Kunju LP, Tomlins SA, Christopherson K, Cortez C, Carskadon S, Siddiqui J, Park K, Mosquera JM, Pestano GA, Rubin MA, Chinnaiyan AM, Palanisamy N - Mod. Pathol. (2013)

Bottom Line: Of the 81 ERG-positive cases, PTEN loss was confirmed in 35 (15%) cases by fluorescence in situ hybridization (FISH).SPINK1 expression was found to be mutually exclusive with ERG expression; however, we identified two cases, of which one showed concomitant expression of ERG and SPINK1 in the same tumor foci, and in the second case ERG and SPINK1 were seen in two independent foci of the same tumor nodule.Further studies are required to understand the molecular heterogeneity of cases with concomitant ERG-SPINK1 expression.

View Article: PubMed Central - PubMed

Affiliation: Michigan Center for Translational Pathology, Ann Arbor, MI, USA.

ABSTRACT
Identification of new molecular markers has led to the molecular classification of prostate cancer based on driving genetic lesions. The translation of these discoveries for clinical use necessitates the development of simple, reliable and rapid detection systems to screen patients for specific molecular aberrations. We developed two dual-color immunohistochemistry-based assays for the simultaneous assessment of ERG-PTEN and ERG-SPINK1 in prostate cancer. A total of 232 cases from 184 localized and 48 metastatic prostate cancers were evaluated for ERG-PTEN and 284 cases from 228 localized and 56 metastatic prostate cancers were evaluated for ERG-SPINK1. Of the 232 cases evaluated for ERG-PTEN, 81 (35%) ERG-positive and 77 (33%) PTEN-deleted cases were identified. Of the 81 ERG-positive cases, PTEN loss was confirmed in 35 (15%) cases by fluorescence in situ hybridization (FISH). PTEN status was concordant in 203 cases (sensitivity 90% and specificity 87%; P<0.0001) by both immunohistochemisty and FISH; however, immunohistochemisty could not distinguish between heterozygous and homozygous deletion status of PTEN. Of the 284 cases evaluated for ERG-SPINK1, 111 (39%) cases were positive for ERG. In the remaining 173 ERG-negative cases, SPINK1 was positive in 26 (9%) cases. SPINK1 expression was found to be mutually exclusive with ERG expression; however, we identified two cases, of which one showed concomitant expression of ERG and SPINK1 in the same tumor foci, and in the second case ERG and SPINK1 were seen in two independent foci of the same tumor nodule. Unlike the homogenous ERG staining in cancer tissues, heterogeneous SPINK1 staining was observed in the majority of the cases. Further studies are required to understand the molecular heterogeneity of cases with concomitant ERG-SPINK1 expression. Automated dual ERG-PTEN and ERG-SPINK1 immunohistochemisty assays are simple, reliable and portable across study sites for the simultaneous assessment of these proteins in prostate cancer.

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Evaluation of ERG and SPINK1 by dual immunohistochemistry in prostate cancerProstate cancer tissues with positive expression of ERG and no expression of SPINK1 (40X) (A&B). ERG and SPINK1 dual immunohistochemisty in a prostate cancer tissue demonstrating diffuse SPINK1 (blue) (C&D) expression and no expression of ERG (brown) (immunohistochemisty, 40X). Heterogeneous pattern of SPINK1 expression in minute cancer foci (immunohistochemisty, 40X). Note ERG staining of endothelial cells, used as positive internal control (E&F).
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Figure 2: Evaluation of ERG and SPINK1 by dual immunohistochemistry in prostate cancerProstate cancer tissues with positive expression of ERG and no expression of SPINK1 (40X) (A&B). ERG and SPINK1 dual immunohistochemisty in a prostate cancer tissue demonstrating diffuse SPINK1 (blue) (C&D) expression and no expression of ERG (brown) (immunohistochemisty, 40X). Heterogeneous pattern of SPINK1 expression in minute cancer foci (immunohistochemisty, 40X). Note ERG staining of endothelial cells, used as positive internal control (E&F).

Mentions: In all evaluable cores vascular endothelial cells and/or lymphocytes stained positive for ERG protein. One hundred and eleven ERG positive cases were identified including 95 (42%) localized and 16 (29%) metastatic prostate carcinomas (Table 5). Three out of 111 ERG-positive patients demonstrated heterogeneous staining while the remaining 108 had uniform staining in cancer tissues (Figure 2, A and B). In one patient, ERG heterogeneity was recorded between discrete tumor nodules within the prostate gland; in a second patient ERG heterogeneity was observed between metastatic sites. A third patient demonstrated ERG staining at one metastatic nodule in the liver while all the other metastatic sites, including a second liver metastases, were negative.


Novel dual-color immunohistochemical methods for detecting ERG-PTEN and ERG-SPINK1 status in prostate carcinoma.

Bhalla R, Kunju LP, Tomlins SA, Christopherson K, Cortez C, Carskadon S, Siddiqui J, Park K, Mosquera JM, Pestano GA, Rubin MA, Chinnaiyan AM, Palanisamy N - Mod. Pathol. (2013)

Evaluation of ERG and SPINK1 by dual immunohistochemistry in prostate cancerProstate cancer tissues with positive expression of ERG and no expression of SPINK1 (40X) (A&B). ERG and SPINK1 dual immunohistochemisty in a prostate cancer tissue demonstrating diffuse SPINK1 (blue) (C&D) expression and no expression of ERG (brown) (immunohistochemisty, 40X). Heterogeneous pattern of SPINK1 expression in minute cancer foci (immunohistochemisty, 40X). Note ERG staining of endothelial cells, used as positive internal control (E&F).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3672354&req=5

Figure 2: Evaluation of ERG and SPINK1 by dual immunohistochemistry in prostate cancerProstate cancer tissues with positive expression of ERG and no expression of SPINK1 (40X) (A&B). ERG and SPINK1 dual immunohistochemisty in a prostate cancer tissue demonstrating diffuse SPINK1 (blue) (C&D) expression and no expression of ERG (brown) (immunohistochemisty, 40X). Heterogeneous pattern of SPINK1 expression in minute cancer foci (immunohistochemisty, 40X). Note ERG staining of endothelial cells, used as positive internal control (E&F).
Mentions: In all evaluable cores vascular endothelial cells and/or lymphocytes stained positive for ERG protein. One hundred and eleven ERG positive cases were identified including 95 (42%) localized and 16 (29%) metastatic prostate carcinomas (Table 5). Three out of 111 ERG-positive patients demonstrated heterogeneous staining while the remaining 108 had uniform staining in cancer tissues (Figure 2, A and B). In one patient, ERG heterogeneity was recorded between discrete tumor nodules within the prostate gland; in a second patient ERG heterogeneity was observed between metastatic sites. A third patient demonstrated ERG staining at one metastatic nodule in the liver while all the other metastatic sites, including a second liver metastases, were negative.

Bottom Line: Of the 81 ERG-positive cases, PTEN loss was confirmed in 35 (15%) cases by fluorescence in situ hybridization (FISH).SPINK1 expression was found to be mutually exclusive with ERG expression; however, we identified two cases, of which one showed concomitant expression of ERG and SPINK1 in the same tumor foci, and in the second case ERG and SPINK1 were seen in two independent foci of the same tumor nodule.Further studies are required to understand the molecular heterogeneity of cases with concomitant ERG-SPINK1 expression.

View Article: PubMed Central - PubMed

Affiliation: Michigan Center for Translational Pathology, Ann Arbor, MI, USA.

ABSTRACT
Identification of new molecular markers has led to the molecular classification of prostate cancer based on driving genetic lesions. The translation of these discoveries for clinical use necessitates the development of simple, reliable and rapid detection systems to screen patients for specific molecular aberrations. We developed two dual-color immunohistochemistry-based assays for the simultaneous assessment of ERG-PTEN and ERG-SPINK1 in prostate cancer. A total of 232 cases from 184 localized and 48 metastatic prostate cancers were evaluated for ERG-PTEN and 284 cases from 228 localized and 56 metastatic prostate cancers were evaluated for ERG-SPINK1. Of the 232 cases evaluated for ERG-PTEN, 81 (35%) ERG-positive and 77 (33%) PTEN-deleted cases were identified. Of the 81 ERG-positive cases, PTEN loss was confirmed in 35 (15%) cases by fluorescence in situ hybridization (FISH). PTEN status was concordant in 203 cases (sensitivity 90% and specificity 87%; P<0.0001) by both immunohistochemisty and FISH; however, immunohistochemisty could not distinguish between heterozygous and homozygous deletion status of PTEN. Of the 284 cases evaluated for ERG-SPINK1, 111 (39%) cases were positive for ERG. In the remaining 173 ERG-negative cases, SPINK1 was positive in 26 (9%) cases. SPINK1 expression was found to be mutually exclusive with ERG expression; however, we identified two cases, of which one showed concomitant expression of ERG and SPINK1 in the same tumor foci, and in the second case ERG and SPINK1 were seen in two independent foci of the same tumor nodule. Unlike the homogenous ERG staining in cancer tissues, heterogeneous SPINK1 staining was observed in the majority of the cases. Further studies are required to understand the molecular heterogeneity of cases with concomitant ERG-SPINK1 expression. Automated dual ERG-PTEN and ERG-SPINK1 immunohistochemisty assays are simple, reliable and portable across study sites for the simultaneous assessment of these proteins in prostate cancer.

Show MeSH
Related in: MedlinePlus