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ETS gene aberrations in atypical cribriform lesions of the prostate: Implications for the distinction between intraductal carcinoma of the prostate and cribriform high-grade prostatic intraepithelial neoplasia.
Am J Surg Pathol. 2010 Apr; 34(4):478-85.AJ

Abstract

BACKGROUND

Atypical cribriform lesions (ACLs) of the prostate consist of cribriform glands lined with cytologically malignant cells with partial or complete basal cell lining. It may represent cribriform "high-grade prostatic intraepithelial neoplasia" (HGPIN) or "intraductal carcinoma of the prostate" (IDC-P), which is almost always associated with clinically aggressive prostate carcinoma (PCa). Distinction between these 2 lesions has profound clinical significance, especially on needle biopsies. However, there are lesions that do not fully satisfy the criteria for IDC-P yet are worse than typical HGPIN and are difficult to distinguish based on morphologic criteria alone.

METHODS

To better understand the biologic and molecular basis of distinction between cribriform HGPIN and IDC, we used break-apart fluorescence in-situ hybridization assay to assess ETS gene aberrations, a specific and commonest molecular alteration involving PCa, in a cohort of 16 isolated ACL, presumed to be an isolated cribriform HGPIN, and 45 carcinoma-associated ACL (ACL-PCa) on radical prostatectomy specimens, presumed to be spectrum of IDC-P. The latter was further divided into 2 groups: group A with marked nuclear atypia (nuclear size 6xnormal or larger) and/or comedonecrosis (n=21) and group B that did not fulfill these criteria (n=24).

RESULTS

Overall, ERG rearrangement was absent (0 of 16) in isolated cribriform HGPIN, whereas present in 75% (36 of 48) of IDC-P, of which 65% (23 of 36) were through deletion and 35% (13 of 36) through insertion. Notably, 17% (6 of 36) of the IDC-P showed duplication of ERG rearrangement in combination with deletion of 5'-ERG. Hundred percent (34 of 34) of the IDC-P showed concordance of ERG rearrangement status with adjacent invasive carcinoma. There was no difference between the 2 groups of IDC-P lesions regarding prevalence of ERG rearrangement (group A 79% vs. group B 74%) and EDel2+ (20% vs. 15%). No case with ETV1, ETV4, or ETV5 rearrangement was identified.

CONCLUSIONS

Our molecular data suggest that isolated cribriform HGPIN and IDC-P are biologically distinct lesions. Majority of ACL-PCa most likely represent intraductal spread of PCa. There is a significant overlap between IDC-P and HGPIN at the lower grade morphologic spectrum. ERG break-apart fluorescence in-situ hybridization assay provides insight into understanding the molecular basis of cribriform HGPIN and IDC-P and has potential clinical implications in their distinction on needle biopsies.

Authors+Show Affiliations

Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

20220513

Citation

Han, Bo, et al. "ETS Gene Aberrations in Atypical Cribriform Lesions of the Prostate: Implications for the Distinction Between Intraductal Carcinoma of the Prostate and Cribriform High-grade Prostatic Intraepithelial Neoplasia." The American Journal of Surgical Pathology, vol. 34, no. 4, 2010, pp. 478-85.
Han B, Suleman K, Wang L, et al. ETS gene aberrations in atypical cribriform lesions of the prostate: Implications for the distinction between intraductal carcinoma of the prostate and cribriform high-grade prostatic intraepithelial neoplasia. Am J Surg Pathol. 2010;34(4):478-85.
Han, B., Suleman, K., Wang, L., Siddiqui, J., Sercia, L., Magi-Galluzzi, C., Palanisamy, N., Chinnaiyan, A. M., Zhou, M., & Shah, R. B. (2010). ETS gene aberrations in atypical cribriform lesions of the prostate: Implications for the distinction between intraductal carcinoma of the prostate and cribriform high-grade prostatic intraepithelial neoplasia. The American Journal of Surgical Pathology, 34(4), 478-85. https://doi.org/10.1097/PAS.0b013e3181d6827b
Han B, et al. ETS Gene Aberrations in Atypical Cribriform Lesions of the Prostate: Implications for the Distinction Between Intraductal Carcinoma of the Prostate and Cribriform High-grade Prostatic Intraepithelial Neoplasia. Am J Surg Pathol. 2010;34(4):478-85. PubMed PMID: 20220513.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ETS gene aberrations in atypical cribriform lesions of the prostate: Implications for the distinction between intraductal carcinoma of the prostate and cribriform high-grade prostatic intraepithelial neoplasia. AU - Han,Bo, AU - Suleman,Khalid, AU - Wang,Lei, AU - Siddiqui,Javed, AU - Sercia,Linda, AU - Magi-Galluzzi,Cristina, AU - Palanisamy,Nallasivam, AU - Chinnaiyan,Arul M, AU - Zhou,Ming, AU - Shah,Rajal B, PY - 2010/3/12/entrez PY - 2010/3/12/pubmed PY - 2010/4/16/medline SP - 478 EP - 85 JF - The American journal of surgical pathology JO - Am J Surg Pathol VL - 34 IS - 4 N2 - BACKGROUND: Atypical cribriform lesions (ACLs) of the prostate consist of cribriform glands lined with cytologically malignant cells with partial or complete basal cell lining. It may represent cribriform "high-grade prostatic intraepithelial neoplasia" (HGPIN) or "intraductal carcinoma of the prostate" (IDC-P), which is almost always associated with clinically aggressive prostate carcinoma (PCa). Distinction between these 2 lesions has profound clinical significance, especially on needle biopsies. However, there are lesions that do not fully satisfy the criteria for IDC-P yet are worse than typical HGPIN and are difficult to distinguish based on morphologic criteria alone. METHODS: To better understand the biologic and molecular basis of distinction between cribriform HGPIN and IDC, we used break-apart fluorescence in-situ hybridization assay to assess ETS gene aberrations, a specific and commonest molecular alteration involving PCa, in a cohort of 16 isolated ACL, presumed to be an isolated cribriform HGPIN, and 45 carcinoma-associated ACL (ACL-PCa) on radical prostatectomy specimens, presumed to be spectrum of IDC-P. The latter was further divided into 2 groups: group A with marked nuclear atypia (nuclear size 6xnormal or larger) and/or comedonecrosis (n=21) and group B that did not fulfill these criteria (n=24). RESULTS: Overall, ERG rearrangement was absent (0 of 16) in isolated cribriform HGPIN, whereas present in 75% (36 of 48) of IDC-P, of which 65% (23 of 36) were through deletion and 35% (13 of 36) through insertion. Notably, 17% (6 of 36) of the IDC-P showed duplication of ERG rearrangement in combination with deletion of 5'-ERG. Hundred percent (34 of 34) of the IDC-P showed concordance of ERG rearrangement status with adjacent invasive carcinoma. There was no difference between the 2 groups of IDC-P lesions regarding prevalence of ERG rearrangement (group A 79% vs. group B 74%) and EDel2+ (20% vs. 15%). No case with ETV1, ETV4, or ETV5 rearrangement was identified. CONCLUSIONS: Our molecular data suggest that isolated cribriform HGPIN and IDC-P are biologically distinct lesions. Majority of ACL-PCa most likely represent intraductal spread of PCa. There is a significant overlap between IDC-P and HGPIN at the lower grade morphologic spectrum. ERG break-apart fluorescence in-situ hybridization assay provides insight into understanding the molecular basis of cribriform HGPIN and IDC-P and has potential clinical implications in their distinction on needle biopsies. SN - 1532-0979 UR - https://www.unboundmedicine.com/medline/citation/20220513/ETS_gene_aberrations_in_atypical_cribriform_lesions_of_the_prostate:_Implications_for_the_distinction_between_intraductal_carcinoma_of_the_prostate_and_cribriform_high_grade_prostatic_intraepithelial_neoplasia_ L2 - https://doi.org/10.1097/PAS.0b013e3181d6827b DB - PRIME DP - Unbound Medicine ER -