Experimental oral carcinoma of the tongue and buccal mucosa: Possible biologic markers linked to cancers at two anatomic sites

Department of Oral Maxillofacial Pathology, Howard University, 600 W Street, Northwest Washington, DC 20059, USA.
Oral Oncology (Impact Factor: 3.61). 04/2000; 36(2):225-35. DOI: 10.1016/S1368-8375(99)00077-9
Source: PubMed


The application of the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) can initiate and promote the development of oral squamous cell carcinoma of the tongue and buccal mucosa. In this study the level of expression of various markers related to the development of programmed cell death (PCD) in the respective oral carcinomas was analyzed. Sixteen male and female Syrian hamsters (Mesocrietus auratus) were treated with 0.05% DMBA for 16 weeks. Immunohistochemistry was used to observe the expression of p53, proliferating cell nuclear antigen (PCNA), Bcl-2, and nucleosome formation. Single-strand conformational polymorphism (SSCP) for exons 2-9 and sequence analysis of exon 9 of the p53 gene from normal buccal or tongue mucosa as well as the squamous cell carcinomas from the buccal mucosa or the tongue were determined. p53 (wild type) expression was significantly reduced in the tongue dysplastic mucosa or squamous cell carcinoma. The SSCP disclosed banding shifts or new bands in exons 2/3, 4, 8, and 9 for the tongue or buccal oral carcinomas (five of each). In exon 9 the mutation in codon 307 (ala)GCC-GTC(val) was present in the tongue but not in the buccal carcinoma. Other markers included the level of PCNA. PCNA was initially lower in the premalignant tongue lesions but increased in oral squamous cell carcinoma at both sites. In contrast, the amount of nucleosome formation in the tongue carcinomas was less than the level noted for buccal cancers but premalignant dysplasias in the tongue mucosa exhibited higher levels. The inhibitor of PCD, Bcl-2 was lower for dysplasias and carcinomas of the tongue compared to similar lesions of the buccal mucosa. These results indicate that oral carcinomas of different anatomical sites can exhibit differences in growth, oncogene mutation expression, and the development of PCD. The differences in Bcl-2 and nucleosome formation may signify their influence on oncogene expression and growth potential for developing transformed clones and established oral carcinomas.

6 Reads
  • Source
    • "Oral squamous cell carcinoma (OSCC) is a deadly malignancy, accounting for more than 90% of malignant tumors of the oral cavity worldwide [1]. Although there has been considerable progress in the understanding of genetic and molecular alterations related to its development , the exact molecular mechanism underlying its formation as well as progression has yet to be established in the literature [2]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Galectin-3 (Gal3) has been implicated in the development of different tumors because of its involvement in the Wnt signaling pathway by promoting beta-catenin translocation into the nucleus. The APC protein, a negative regulator of this pathway, has been strongly implicated in the development of colon cancer, but still has an undetermined role in the formation of oral cancer. Therefore, this study aimed to evaluate the relationship between Gal3, the Wnt signaling pathway, and APC expression in dysplasias and carcinomas developed experimentally in mice. Sixty galectin-3-deficient (Gal3(-/-)) and 60 wild-type (Gal3(+/+)) mice were early employed to be treated with the carcinogen 4NQO for 16 weeks and killed at either week 16 or week 32. Tongues were removed, processed and embedded in paraffin blocks. Sections 5 μm thick were made, and then stained by H&E to establish the diagnosis of dysplasia and carcinoma. Sections of 2 μm thickness were made to detect APC expression in these lesions by immunohistochemistry. Oral carcinogenesis occurred in both groups of mice, but no statistical difference was reached. APC expression was exclusively seen in the cytoplasm of all lesions studied. In the intragroup analysis, the majority of dysplasias and carcinomas exhibiting higher APC immunoreactivity was observed in Gal3(-/-) mice compared to Gal3(+/+) mice, but no significant difference was found. However, a statistical difference was only observed between dysplastic lesions from two mice. Our results showed that neither the absence of Gal3 nor the APC protein appears to play a role in malignant transformation of the tongue.
    Full-text · Article · Jul 2014 · International journal of clinical and experimental pathology
  • Source
    • "Some of the nuclear cell proliferation antigens associated with oral cancer are P120 (Schliephake, 2003), Ki-67/ MIB (Schliephake, 2003;Tumuluri et al., 2002), AgNOR (Schliephake, 2003), and Skp2 (Schliephake, 2003). It has been shown that levels of proliferating cell nuclear antigen are increased in an experimental model (Schwartz et al., 2000). It has been suggested to use AgNOR and Ki-67 analyses to determine proliferative states of epithelial cells in oral cancer (Teresa et al., 2007;Costa et al., 1999). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Oral and oropharynx cancer is the seventh most common form of cancer worldwide and is projected to increase by over 60% in the next two decades (Mathers and Loncar, 2006). Around half of the patients detected with oral cancer will die within 5 years of initial diagnosis. The high mortality rate can be attributed to technological limitations, which allows detection of oral cancer with confidence only in the advanced stage. A clear understanding of oral cancer-associated risk factors and early detection of oral cancer would be critical in improving survival. Treatment planning, patient stratification, and prognosis for patients with oral cancer are mainly based on tumor, node, and metastasis (TNM) classification (Patel and Shah, 2005), which is not perfect. Two-step carcinogenesis of the oral mucosa is well established, which postulates development of oral cancer from a precursor lesion. However, there is clinical evidence that contradicts the two-step carcinogenesis model for oral cancer (Reibel, 2003). These traditional clinical methods are subjective at the best, and are not sensitive for early detection of oral cancer, and have a very limited scope in predicting the aggressiveness of the tumor and identifying high-risk patients. Early detection of oral cancer by sensitive monitoring of tumor-specific markers should help in disease management and improving survival. Oral cancer progression results from the complex interaction of various genetic and environmental factors. These genetic factors modulate various molecular changes, and monitoring such molecular changes offers a tremendous opportunity for early detection, and thereby management of oral cancer therapy. Tumor cells shed by primary cancers find their way to the circulatory system, which should allow early detection of cancer. In the progression of a tumor from a homogeneous proliferating clone to a group of heterogeneous subpopulations of cells, the cells generate an entire array of enzymes and surface molecules (Mendelsohn, 1987; Sah et al.,
    Full-text · Chapter · May 2013
  • Source
    • "SCCs can occur in any region of the mouth but SCCs of the tongue show some peculiarities because of their more infiltrative character and their high potential for developing metastases even when the tumor diameter is small. Generally, SCCs exhibit an aggressive clinical course and an unfavorable prognosis [1]; however, in their biologic behavior, oral SCCs are characterized by significant heterogeneity and tumors of the same clinical stage often show differences in clinical course and treatment response [2]. Thus, identification of factors affecting invasion and metastasis and establishment of biomarkers to predict malignant potential and identify different risk groups are of paramount importance. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To examine immunoexpression of matrix metalloproteinase (MMP)-7 and -26 in squamous cell carcinoma (SCC) of the tongue and its relation with cervical metastasis. Twenty-four cases were selected and divided into two groups: a metastatic group (n = 12) and a non-metastatic group (n = 12). Cases were graded as either negative (score 0), positive (score +) or strongly positive (score ++). MMP-7 expression was identical in both groups, with 17% of the cases graded as score 0, 50% as score + and 33% as score ++. MMP-26 expression was 25% score 0, 8% score + and 67% score ++ in the metastatic group, and 8% score 0, 50% score + and 42% score ++ in the non-metastatic group. Statistical analysis showed no differences between the studied groups and no correlations between proteins. MMP-7 and -26 immunostaining is not a useful indicator of the metastatic potential of SCCs of the tongue. However, the role of these proteins in the process of invasion and metastasis cannot be ruled out since their more marked presence along the tumor invasion front compared to more central areas of the tumors indicates higher secretion of these proteases in this region, facilitating the invasion process.
    Full-text · Article · Jul 2010 · Acta odontologica Scandinavica
Show more