Signal transduction proteins in tumors from Puerto Rican and Caucasian gastric adenocarcinoma patients: expression differences with potential for specific targeted therapies.
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.
Cangiano
José
J
Ponce School of Medicine, Ponce Oncologic Hospital, Ponce, Puerto Rico.
Centeno
Barbara A
BA
Garrett
Christopher R
CR
Cáceres
William
W
de Jesús
Ana
A
Lee
Ji-Hyun
JH
Pavía
Orestes
O
Jove
Richard
R
Báez
Luis
L
Sullivan
Daniel M
DM
Muro-Cacho
Carlos A
CA
Muñoz-Antonia
Teresita
T
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
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