Loss of Fhit expression in testicular germ cell tumors and intratubular germ cell neoplasia. 2002

Eduardo Eyzaguirre, and Zoran Gatalica
Department of Pathology, Division of Surgical Pathology, The University of Texas Medical Branch, Galveston, Texas, USA.

The FHIT gene, located at human chromosome 3p14.2, is frequently deleted in a number of human cancers, and interstitial deletions at this site were recently described in a significant proportion (41%) of testicular germ cell tumors. We studied the expression of Fhit protein in the progression and differentiation of testicular germ cell tumors to further elucidate its role in this type of malignancy. Forty-five patients with testicular germ cell tumors and intratubular germ cell neoplasia (identified in 42/45 cases) were included in the study. Immunohistochemical staining with polyclonal rabbit IgG antibody to Fhit (ZR44, Zymed Laboratories) on formalin-fixed, paraffin-embedded tissues was used. Fhit was constitutively expressed in germ cells, Sertoli cells, and Leydig cells. All 42 cases of intratubular germ cell neoplasia revealed no expression of this protein. No expression of Fhit was observed in any case of pure seminoma or in the seminomatous component of mixed germ cell tumors. Unexpectedly, Fhit expression was frequently (16/18) observed in the glandular tissue of mature teratomatous component of mixed germ cell tumors, despite the absence of Fhit in the intratubular germ cell neoplasia, the presumed precursor lesion. The loss of Fhit expression is a consistent characteristic of intratubular germ cell neoplasia, which suggests a potential role in a maturation/differentiation defect early in the development of testicular germ cell tumors. Likewise, the lack of expression in seminomas is supportive of this view. However, re-expression of Fhit in well-differentiated glandular epithelium of teratomatous component of mixed germ cell tumors suggests that there is no loss of FHIT gene in this subset of neoplasia but rather that Fhit protein expression is differently regulated through the phases of germ cell tumor progression.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008297 Male Males
D009363 Neoplasm Proteins Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm. Proteins, Neoplasm
D002278 Carcinoma in Situ A lesion with cytological characteristics associated with invasive carcinoma but the tumor cells are confined to the epithelium of origin, without invasion of the basement membrane. Carcinoma, Intraepithelial,Carcinoma, Preinvasive,Intraepithelial Neoplasms,Neoplasms, Intraepithelial,Intraepithelial Carcinoma,Intraepithelial Neoplasm,Neoplasm, Intraepithelial,Preinvasive Carcinoma
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012670 Seminiferous Epithelium The epithelium lining the seminiferous tubules composed of primary male germ cells (SPERMATOGONIA) and supporting SERTOLI CELLS. As SPERMATOGENESIS proceeds, the developing germ cells migrate toward the lumen. The adluminal compartment, the inner two thirds of the tubules, contains SPERMATOCYTES and the more advanced germ cells. Epithelium, Seminiferous,Epitheliums, Seminiferous,Seminiferous Epitheliums
D013736 Testicular Neoplasms Tumors or cancer of the TESTIS. Germ cell tumors (GERMINOMA) of the testis constitute 95% of all testicular neoplasms. Cancer of Testis,Cancer of the Testes,Testicular Cancer,Testicular Neoplasm,Testicular Tumor,Testis Cancer,Cancer of the Testis,Neoplasms, Testicular,Neoplasms, Testis,Testicular Tumors,Testis Neoplasms,Tumor of Rete Testis,Cancer, Testicular,Cancer, Testis,Cancers, Testicular,Cancers, Testis,Neoplasm, Testicular,Neoplasm, Testis,Rete Testis Tumor,Rete Testis Tumors,Testicular Cancers,Testis Cancers,Testis Neoplasm,Testis Tumor, Rete,Testis Tumors, Rete,Tumor, Testicular,Tumors, Testicular
D016147 Genes, Tumor Suppressor Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible. Antioncogenes,Cancer Suppressor Genes,Emerogenes,Genes, Cancer Suppressor,Genes, Growth Suppressor,Genes, Metastasis Suppressor,Growth Suppressor Genes,Metastasis Suppressor Genes,Tumor Suppressor Genes,Anti-Oncogenes,Genes, Onco-Suppressor,Oncogenes, Recessive,Tumor Suppressing Genes,Anti Oncogenes,Anti-Oncogene,Antioncogene,Cancer Suppressor Gene,Emerogene,Gene, Cancer Suppressor,Gene, Growth Suppressor,Gene, Metastasis Suppressor,Gene, Onco-Suppressor,Gene, Tumor Suppressing,Gene, Tumor Suppressor,Genes, Onco Suppressor,Genes, Tumor Suppressing,Growth Suppressor Gene,Metastasis Suppressor Gene,Onco-Suppressor Gene,Onco-Suppressor Genes,Oncogene, Recessive,Recessive Oncogene,Recessive Oncogenes,Suppressor Gene, Cancer,Suppressor Gene, Growth,Suppressor Gene, Metastasis,Suppressor Genes, Cancer,Suppressor Genes, Growth,Suppressor Genes, Metastasis,Tumor Suppressing Gene,Tumor Suppressor Gene
D017766 Acid Anhydride Hydrolases A group of enzymes that catalyze the hydrolysis of diphosphate bonds in compounds such as nucleoside di- and tri-phosphates, and sulfonyl-containing anhydrides such as adenylylsulfate. (Enzyme Nomenclature, 1992) EC 3.6. Anhydride Hydrolases, Acid,Hydrolases, Acid Anhydride
D018237 Germinoma A malignant neoplasm of the germinal tissue of the GONADS; MEDIASTINUM; or pineal region. Germinomas are uniform in appearance, consisting of large, round cells with vesicular nuclei and clear or finely granular eosinophilic-staining cytoplasm. (Stedman, 265th ed; from DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, pp1642-3) Germinomas

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