TY - JOUR
T1 - Signal transduction proteins in tumors from puerto rican and caucasian gastric adenocarcinoma patients
T2 - Expression differences with potential for specific targeted therapies
AU - Cangiano, José
AU - Centeno, Barbara A.
AU - Garrett, Christopher R.
AU - Cáceres, William
AU - De Jesús, Ana
AU - Lee, Ji Hyun
AU - Pavía, Orestes
AU - Jove, Richard
AU - Báez, Luis
AU - Sullivan, Daniel M.
AU - Muro-Cacho, Carlos A.
AU - Muñoz-Antonia, Teresita
N1 - Funding Information:
Acknowledgments Anita C. Bruce contributed editorial support. This study was partially supported by a National Cancer Institute Partnership Grant (P20 CA91353) to the H. Lee Moffitt and Puerto Rico Cancer Centers.
PY - 2008/8
Y1 - 2008/8
N2 - 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.
AB - 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.
KW - Cyclin D1
KW - Epidermal growth factor receptor
KW - Gastric adenocarcinoma
KW - Her2/neu
KW - Stat3
KW - Stomach cancer
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U2 - 10.1007/s10620-007-0118-5
DO - 10.1007/s10620-007-0118-5
M3 - Article
C2 - 18224443
AN - SCOPUS:46449087606
SN - 0163-2116
VL - 53
SP - 2090
EP - 2100
JO - Digestive diseases and sciences
JF - Digestive diseases and sciences
IS - 8
ER -