title: Signal transduction proteins in tumors from Puerto Rican and Caucasian gastric adenocarcinoma patients: expression differences with potential for specific targeted therapies.
abstract: Overexpression of the HER2/NEU gene is associated with aggressive behavior and poor prognosis in breast cancer, making the Her2/neu protein a directed-therapy target. Tumors of two Puerto Rican (PR) patients overexpressed Her2/neu and resulting partial clinical responses motivated us to compare Her2/neu expression in PR (n = 101) and Caucasian non-Hispanic (n = 95) patients. Immunohistochemistry of tumors showed overexpression of p-Stat3, Cyclin D1, and Her2/neu, compared to non-neoplastic mucosa. Her2/neu and EGF-R protein levels were statistically significantly different with higher levels of both proteins in the PR group. Importantly, Her2/neu expression was strong and diffuse in tumors with signet-ring morphology, while other histo-pathological subtypes showed higher intra-tumoral Her2/neu heterogeneity than typically observed in breast cancer. Targeted therapies in gastric cancer directed at EGF-R and Hers-2/neu pathways warrant further investigation. These therapies may be especially effective in PR patients and in patients with signet-ring cell morphologies with a dismal prognosis.
authors.affiliation: Ponce School of Medicine, Ponce Oncologic Hospital, Ponce, Puerto Rico.
authors.forename: José
authors.initials: J
authors.lastname: Cangiano
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Centeno
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Garrett
authors.forename: William
authors.initials: W
authors.lastname: Cáceres
authors.forename: Ana
authors.initials: A
authors.lastname: de Jesús
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Orestes
authors.initials: O
authors.lastname: Pavía
authors.forename: Richard
authors.initials: R
authors.lastname: Jove
authors.forename: Luis
authors.initials: L
authors.lastname: Báez
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Sullivan
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Muro-Cacho
authors.forename: Teresita
authors.initials: T
authors.lastname: Muñoz-Antonia
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis*; D000230:Adenocarcinoma / Q000737:chemistry / Q000208:ethnology / Q000473:pathology / Q000628:therapy; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018279:Carcinoma, Signet Ring Cell / Q000737:chemistry / Q000188:drug therapy / Q000208:ethnology / Q000473:pathology; D056741:Cyclin D; D016213:Cyclins / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D005431:Florida; D006630:Hispanic or Latino; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018579:Patient Selection; D011647:Puerto Rico; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012189:Retrospective Studies; D050796:STAT3 Transcription Factor / Q000032:analysis; D013274:Stomach Neoplasms / Q000737:chemistry / Q000208:ethnology / Q000473:pathology / Q000628:therapy; D044465:White People
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D056741:Cyclin D; D016213:Cyclins; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human