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The role of HER2/neu overexpression/amplification in the progression of ductal carcinoma in situ to invasive carcinoma of the breast.
Mod Pathol. 2002 Dec; 15(12):1318-25.MP

Abstract

HER2/neu overexpression/amplification is seen more frequently in ductal carcinoma in situ, particularly high-grade ductal carcinoma in situ (50-60%), than in invasive ductal carcinoma of the breast (25-30%). To date, however, the role of HER2/neu in the progression of in situ to invasive disease has not been clarified. Two hundred fifty-one breast tumors were retrieved from the pathology files at Mount Sinai Hospital. These included 91 cases of ductal carcinoma in situ, 136 cases of invasive ductal carcinomas with associated ductal carcinoma in situ, and 24 cases of pure invasive carcinomas. All cases were reviewed and stained with two monoclonal antibodies to HER2/neu (CB11 and TAB250). Immunohistochemical staining was recorded using a semiquantitative scoring system (1). Representative cases were also investigated using fluorescence in situ hybridization. HER2/neu protein overexpression (defined as immunohistochemical staining with score of >or=5) was seen in 34% of cases of pure ductal carcinoma in situ, 17% of invasive carcinomas with associated ductal carcinoma in situ, and 12.5% of pure invasive carcinomas (P =.01). Sixty percent of cases of high-grade ductal carcinoma in situ showed HER2/neu protein overexpression, versus 29% of high-grade invasive carcinomas with associated ductal carcinoma in situ and 22% of high-grade pure invasive ductal carcinomas (P =.02). The concordance between the immunohistochemical staining in the in situ and invasive components of individual tumors was 90%. Thirty-three cases were also evaluated by fluorescence in situ hybridization and showed concordance between the immunohistochemical results and the degree of gene amplification in 91% of cases, whereas 3 of 33 cases showed HER2/neu gene amplification (HER2/CEP17 = 2.3-3.7) by fluorescence in situ hybridization in the absence of positive immunohistochemical staining. One case showed HER2/neu gene amplification in the associated ductal carcinoma in situ (HER2/CEP17 ratio = 6.5), with no evidence of gene amplification in the invasive tumor (HER2/CEP17 ratio = 1.14). Multiple genetic events are required for the development of an invasive phenotype. The findings from this study suggest that the genetic event of HER2/neu gene amplification/protein overexpression may not play a key role in the progression of ductal carcinoma in situ to invasive carcinoma and that other molecular alterations may be more important in the initiation of invasion in ductal carcinoma of the breast.

Authors+Show Affiliations

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12481013

Citation

Latta, E K., et al. "The Role of HER2/neu Overexpression/amplification in the Progression of Ductal Carcinoma in Situ to Invasive Carcinoma of the Breast." Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, vol. 15, no. 12, 2002, pp. 1318-25.
Latta EK, Tjan S, Parkes RK, et al. The role of HER2/neu overexpression/amplification in the progression of ductal carcinoma in situ to invasive carcinoma of the breast. Mod Pathol. 2002;15(12):1318-25.
Latta, E. K., Tjan, S., Parkes, R. K., & O'Malley, F. P. (2002). The role of HER2/neu overexpression/amplification in the progression of ductal carcinoma in situ to invasive carcinoma of the breast. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 15(12), 1318-25.
Latta EK, et al. The Role of HER2/neu Overexpression/amplification in the Progression of Ductal Carcinoma in Situ to Invasive Carcinoma of the Breast. Mod Pathol. 2002;15(12):1318-25. PubMed PMID: 12481013.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of HER2/neu overexpression/amplification in the progression of ductal carcinoma in situ to invasive carcinoma of the breast. AU - Latta,E K, AU - Tjan,S, AU - Parkes,R K, AU - O'Malley,F P, PY - 2002/12/14/pubmed PY - 2003/4/23/medline PY - 2002/12/14/entrez SP - 1318 EP - 25 JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JO - Mod Pathol VL - 15 IS - 12 N2 - HER2/neu overexpression/amplification is seen more frequently in ductal carcinoma in situ, particularly high-grade ductal carcinoma in situ (50-60%), than in invasive ductal carcinoma of the breast (25-30%). To date, however, the role of HER2/neu in the progression of in situ to invasive disease has not been clarified. Two hundred fifty-one breast tumors were retrieved from the pathology files at Mount Sinai Hospital. These included 91 cases of ductal carcinoma in situ, 136 cases of invasive ductal carcinomas with associated ductal carcinoma in situ, and 24 cases of pure invasive carcinomas. All cases were reviewed and stained with two monoclonal antibodies to HER2/neu (CB11 and TAB250). Immunohistochemical staining was recorded using a semiquantitative scoring system (1). Representative cases were also investigated using fluorescence in situ hybridization. HER2/neu protein overexpression (defined as immunohistochemical staining with score of >or=5) was seen in 34% of cases of pure ductal carcinoma in situ, 17% of invasive carcinomas with associated ductal carcinoma in situ, and 12.5% of pure invasive carcinomas (P =.01). Sixty percent of cases of high-grade ductal carcinoma in situ showed HER2/neu protein overexpression, versus 29% of high-grade invasive carcinomas with associated ductal carcinoma in situ and 22% of high-grade pure invasive ductal carcinomas (P =.02). The concordance between the immunohistochemical staining in the in situ and invasive components of individual tumors was 90%. Thirty-three cases were also evaluated by fluorescence in situ hybridization and showed concordance between the immunohistochemical results and the degree of gene amplification in 91% of cases, whereas 3 of 33 cases showed HER2/neu gene amplification (HER2/CEP17 = 2.3-3.7) by fluorescence in situ hybridization in the absence of positive immunohistochemical staining. One case showed HER2/neu gene amplification in the associated ductal carcinoma in situ (HER2/CEP17 ratio = 6.5), with no evidence of gene amplification in the invasive tumor (HER2/CEP17 ratio = 1.14). Multiple genetic events are required for the development of an invasive phenotype. The findings from this study suggest that the genetic event of HER2/neu gene amplification/protein overexpression may not play a key role in the progression of ductal carcinoma in situ to invasive carcinoma and that other molecular alterations may be more important in the initiation of invasion in ductal carcinoma of the breast. SN - 0893-3952 UR - https://www.unboundmedicine.com/medline/citation/12481013/The_role_of_HER2/neu_overexpression/amplification_in_the_progression_of_ductal_carcinoma_in_situ_to_invasive_carcinoma_of_the_breast_ L2 - https://doi.org/10.1097/01.MP.0000038462.62634.B1 DB - PRIME DP - Unbound Medicine ER -