Abstract 4824: The “gatekeeper” function ofDrosophilaSeven-IN-Absentia (SINA) E3 ligase and its human homologs, SIAH1 and SIAH2, is highly conserved for proper RAS signal transduction inDrosophiladevelopment

Abstract Context.—ras gene mutations and expression of its gene product have been described in verrucous and squamous cell carcinomas. Other downstream signal-transduction mediators, extracellular signal-regulated kinases 1 and 2 (ERK-1 and ERK-2) and Raf-1, have not yet been as extensively studied. Objective.—To determine patterns of expression of ERK-1, ERK-2, and Raf-1 in verrucous and squamous cell carcinomas of the upper aerodigestive tract. Design.—Seventeen verrucous carcinomas and 10 squamous cell carcinomas of the upper aerodigestive tract were examined for the immunohistochemical expression of ERK-1, ERK-2, and Raf-1 product. Results.—Raf-1 expression was intensely expressed in the most basal portions of the epithelium in verrucous carcinomas, but was minimally expressed in the suprabasalar areas. Anti-Raf-1 staining of the squamous cell carcinomas was diffuse and patchy throughout the tumor cells and was weak in intensity. There was no geographic preference of staining. The cytoplasmic expression of both ERK-1 and ERK-2 was predominantly negative in the most basal layers of the epithelium in the verrucous carcinomas, but was positive in the suprabasalar region of the epithelium. Immunohistochemical expression of ERK-1 and ERK-2 in the squamous carcinomas was diffuse throughout the tumor. Conclusion.—There is strong correlation of the geographic expression of these mediators of ras signal transduction in verrucous and squamous carcinomas, but the cause of these differences remains unclear at present. The expression of these mediator proteins may have potential for diagnosis, as well as in understanding the biologic behavior of these lesions.

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ras Gene Mutations and Expression of Ras Signal Transduction Mediators in Gastric Adenocarcinomas

Archives of Pathology & Laboratory Medicine ◽

10.5858/2002-126-1096-rgmaeo ◽

2002 ◽

Vol 126 (9) ◽

pp. 1096-1100 ◽

Cited By ~ 1

Author(s):

Jinyoung Yoo ◽

Sonya Y. Park ◽

Robert A. Robinson ◽

Seok Jin Kang ◽

Woong Shick Ahn ◽

...

Keyword(s):

Signal Transduction ◽

Tertiary Care ◽

Immunohistochemical Analysis ◽

Intestinal Type ◽

Ras Gene ◽

Ras Mutations ◽

Korean Patients ◽

Gene Alteration ◽

Gastric Adenocarcinomas ◽

Ras Signal Transduction

Abstract Objective.—To investigate ras gene alteration in human gastric adenocarcinomas and its potential relationship to ras signal transduction mediators. Design.—Genomic DNA from 104 gastric tumors were analyzed by sequencing of polymerase chain reaction–amplified products for the presence of ras mutations. All the samples were further investigated with the use of immunohistochemical analysis for ERK1 and ERK2. Setting.—Tertiary care teaching hospital. Patients.—Seventy patients from a Korean population and 34 from a Midwestern US population composed of white Americans and African Americans. Results.—Fifteen tumors (14%) were positive for either H-ras or K-ras mutation: 9 (13%) of 70 Korean patients and 6 (18%) of 34 US patients. Seven (78%) of the 9 mutated tumors from Korean patients and all 6 (100%) from the US patients were intestinal-type lesions. Either ERK1 and/or ERK2 was overexpressed in 68 samples (65%). No association was established between ras mutations and overexpression of ERK1/2. However, the correlation between ERK1/2 and progression (early vs late) was statistically significant (P = .007). Conclusions.—These data suggest that ras mutations are uncommon in gastric adenocarcinomas and that differing racial and/or geographic mechanisms may not underlie ras gene alteration. Most ras mutations were, however, observed in the group of intestinal-type samples, supporting the different genetic mechanisms of carcinogenesis between the intestinal- and diffuse-type tumors. It is noteworthy that enhanced ERK1/2 activity could be one of the characteristics of tumor invasiveness in gastric cancers.

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