Limits...
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.

Show MeSH

Related in: MedlinePlus

Concomitant expression of ERG and SPINK1 in prostate cancerHematoxylin and Eosin staining of a prostate cancer tissue (A) with expression of both ERG (red) and SPINK1 (brown) in two different adjacent foci (B). Image from the resection of the same case shown in B demonstrating ERG and SPINK1 positivity in adjacent foci with punch holes (X) for tissue microarray biopsies (C). Concomitant expression of ERG (brown) and SPINK1 (red) in the same tumor foci (D&E).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3672354&req=5

Figure 3: Concomitant expression of ERG and SPINK1 in prostate cancerHematoxylin and Eosin staining of a prostate cancer tissue (A) with expression of both ERG (red) and SPINK1 (brown) in two different adjacent foci (B). Image from the resection of the same case shown in B demonstrating ERG and SPINK1 positivity in adjacent foci with punch holes (X) for tissue microarray biopsies (C). Concomitant expression of ERG (brown) and SPINK1 (red) in the same tumor foci (D&E).

Mentions: An interesting finding was noted in a prostatectomy sample with limited tumor represented on a tissue microarray (Figure 3A). Some prostate cancer glands showed expression of ERG; however, one gland present partially towards the edge of the biopsy was SPINK1 positive (Figure 3B). We further explored the patient’s resection with ERG-SPINK1 immunohistochemisty. As seen on the tissue microarray, the tumor showed expression of both ERG and SPINK1 in adjacent, neighboring foci of the same tumor (Figure 3C). Additionally, in another case of localized prostate cancer we observed a concomitant expression of ERG and SPINK1 in the same focus of the tumor (Figure 3, D and E). Because of the advantages of this novel dual immunohistochemisty procedure, to the best of our knowledge this is the first observation of a rare subset of prostate cancer with concomitant rearrangement of ERG and expression of SPINK1 either in the same or different cancer foci.


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)

Concomitant expression of ERG and SPINK1 in prostate cancerHematoxylin and Eosin staining of a prostate cancer tissue (A) with expression of both ERG (red) and SPINK1 (brown) in two different adjacent foci (B). Image from the resection of the same case shown in B demonstrating ERG and SPINK1 positivity in adjacent foci with punch holes (X) for tissue microarray biopsies (C). Concomitant expression of ERG (brown) and SPINK1 (red) in the same tumor foci (D&E).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Concomitant expression of ERG and SPINK1 in prostate cancerHematoxylin and Eosin staining of a prostate cancer tissue (A) with expression of both ERG (red) and SPINK1 (brown) in two different adjacent foci (B). Image from the resection of the same case shown in B demonstrating ERG and SPINK1 positivity in adjacent foci with punch holes (X) for tissue microarray biopsies (C). Concomitant expression of ERG (brown) and SPINK1 (red) in the same tumor foci (D&E).
Mentions: An interesting finding was noted in a prostatectomy sample with limited tumor represented on a tissue microarray (Figure 3A). Some prostate cancer glands showed expression of ERG; however, one gland present partially towards the edge of the biopsy was SPINK1 positive (Figure 3B). We further explored the patient’s resection with ERG-SPINK1 immunohistochemisty. As seen on the tissue microarray, the tumor showed expression of both ERG and SPINK1 in adjacent, neighboring foci of the same tumor (Figure 3C). Additionally, in another case of localized prostate cancer we observed a concomitant expression of ERG and SPINK1 in the same focus of the tumor (Figure 3, D and E). Because of the advantages of this novel dual immunohistochemisty procedure, to the best of our knowledge this is the first observation of a rare subset of prostate cancer with concomitant rearrangement of ERG and expression of SPINK1 either in the same or different cancer foci.

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