title: Status of HER2 amplification, polysomy 17 and histopathological features of 425 Pakistani breast cancer patients.
abstract: HER2 gene amplification in invasive breast cancer is a robust predictive marker for response to transtuzumab therapy. This study was undertaken to measure concordance between immunohistochemistry (IHC) and FISH for HER2 gene amplification in invasive breast tumors, as well as the presence of polysomy 17 and possible correlation with demographics and histopathological variables, including ER and PR positivity. A total of 425 cases of infiltrating carcinoma of breast (99% IDC-NOS) were studied. HER2 over expression was tested by IHC and FISH methods. Association between IHC and FISH in both subsets was calculated by amplification ratio including polysomy 17. Out of 425 specimens, 128 (30%) were positive for HER2 amplification by FISH test, whereas only 78 (24%) tumors with 2+  expression showed amplification. In contrast, 39 (74%) demonstrated 3+  IHC score and HER2 gene amplification. The histological variables including tumor size, tumor type, and lymph node involvement did not influence the outcome of FISH analysis. The ER and PR status showed significantly greater positivity in patients negative for HER2 amplification. Polysomy 17 was detected in 23.7% patients and was positively associated with ER and PR expression (P= <0.05). Our study showed a concordance of 24% between 2+  IHC and FISH amplification, while in 3+  IHC cases the concordance was 74%. Significant links of HER2 amplification was seen with ER andPR negativity and higher tumor grade. In addition, non-significant correlations were noted with other variables like tumor type, size and lymph node status.
authors.affiliation: Department of Pathology and Microbiology, Medical College, The Aga Khan University, Pakistan.
authors.forename: Tariq
authors.initials: T
authors.lastname: Moatter
authors.forename: Muniba
authors.initials: M
authors.lastname: Aban
authors.forename: Waseem
authors.initials: W
authors.lastname: Iqbal
authors.forename: Iqbal
authors.initials: I
authors.lastname: Azam
authors.forename: Afshan
authors.initials: A
authors.lastname: Pervaiz
authors.forename: Farjad
authors.initials: F
authors.lastname: Siddiqui
authors.forename: Farzana
authors.initials: F
authors.lastname: Murad
authors.forename: Shahid
authors.initials: S
authors.lastname: Pervez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D058674:Chromosome Duplication; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D010154:Pakistan; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068878:Trastuzumab; C508053:ERBB2 protein, human