Tetsuyo Odajima

Expression of E-cadherin, α-catenin, and β-catenin in the process of lymph node metastasis in oral squamous cell carcinoma

Regional lymph node metastasis is a very important prognostic indicator. In the metastatic process, reduction in cell to cell adhesion including E-cadherin–catenin cell adhesion complex is an essential step. We investigated immunohistochemical expression of E-cadherin, α-catenin and β-catenin in 159 tissue samples from patients with oral squamous cell carcinoma and examined the correlation between their expressions and the presence of regional lymph node metastasis. Significantly greater reduction in expression levels of E-cadherin, α-catenin and β-catenin was found in the metastatic group (n=64) compared to the nonmetastatic group (n=95) (P=0.007, 0.001, 0.001, respectively). However, there was no significant correlation between their expressions and the features of the regional metastasis, the number of metastatic lymph nodes or the presence of extracapsular metastasis. These data suggest that evaluation of the immunohistochemical expression of E-cadherin, α-catenin and β-catenin is extremely valuable for the diagnosis of metastatic occurrence.

Significance of glutathione S-transferase-π as a tumor marker in patients with oral cancer

Background. The authors analyzed the clinical usefulness of glutathione‐S‐transferase‐π (GST‐π) as a tumor marker in patients with oral cancer.

Combined expression of p53, cyclin D1 and epidermal growth factor receptor improves estimation of prognosis in curatively resected oral cancer

p53, cyclin D1 and epidermal growth factor receptor (EGFR) are molecular markers that regulate the cell cycle or cell growth and play important roles in tumor development and progression. In this study, we examined the impact of immunohistochemical expression of these markers on tumor progression in 140 oral cancers. p53, cyclin D1 and EGFR were expressed in 64 cases (46%), 54 cases (39%) and 54 cases (39%), respectively, but there was no inter-relationship between any two of these markers. In the association of these markers with clinicopathological features, EGFR expression alone was significantly associated with poor differentiation (P=0.0008) and invasive growth pattern (P=0.0003). Any of these markers, including EGFR, had no significant impact on survival. Coexpression of all these markers, however, was significantly associated with invasive growth pattern (P=0.0149) and shortened survival (P=0.0181), and was a significant and independent unfavorable prognostic factor (P=0.0002), along with tumor size (P=0.0040), nodal metastasis (P=0.0137) and growth pattern (P=0.0017) in a multivariate analysis. Simultaneous coexpression of these markers in oral cancers might prove to be a useful indicator for identification of low- or high-risk patients.

Expression of Rb, pRb2/p130, p53, and p16 proteins in malignant melanoma of oral mucosa

We previously reported that pRb2/p130 gene, one of the Rb family members, was immunohistochemically abundantly expressed in well-differentiated oral squamous cell carcinomas, whereas in undifferentiated ones the expression was low. Oral malignant melanoma is extremely rare, however the prognosis is poor because it tends to locally invade tissue or metastasize and its biological behavior appears to be different from cutaneous malignant melanoma. The present study dealt with the expression of pRb2/p130, Rb, p53, and p16 in 13 cases of malignant melanoma of oral mucosa as revealed by immunohistochemical staining. The stage classification of the 13 patients was as follows; stage II: eight patients, stage III: three patients, and stage IV: two patients. pRb2/p130 was expressed in only two stage II-cases, neither of which have shown any evidence of recurrence or metastasis for over 14 years. Positive staining for Rb was found in three cases consisting of one stage II-case, one stage III-case, and one stage IV-case. p53 was expressed in two cases, one a stage II and the other a stage IV. Positive staining for p16 was found in seven cases consisting of four stage II-cases, two stage III-cases, and one stage IV-case. pRb2/p130 may be inversely correlated with the malignancy of oral malignant melanoma, but further study is needed.

pRb2/p130 protein expression is correlated with clinicopathologic findings in patients with oral squamous cell carcinoma.

pRb2/p130 is one of the retinoblastoma (Rb) gene family and a suppressor oncogene. Immunohistochemically, the expression of pRb2/p130 was reported to be correlated inversely with the degree of malignancy in lung carcinoma and endometrial carcinoma. In the current study, the correlation between expression of pRb2/p130 and clinicopathologic factors in oral squamous cell carcinoma was investigated.

Immunohistochemical investigation of new suppressor oncogene p130 in oral squamous cell carcinoma

Abstract New onco-suppressor gene p130 is one of the Rb family forms and is reported to undergo allelic loss in hepatocellular, prostate, and breast carcinomas; however, no report of p130 has been made in oral tumors. The present study dealt with the expression of p130 and Rb proteins by immunohistochemical staining in oral squamous cell carcinomas ( n =110) and oral mucosa. The site of the carcinomas included tongue ( n =48), gingiva ( n =32), oral floor of the mouth ( n =15), oropharynx ( n =6), buccal mucosa ( n =5), and others ( n =4). Histologically there were 65 well-differentiated carcinomas, 33 moderately differentiated carcinomas, and 12 poorly differentiated ones. Positive staining for p130 and Rb was localized to suprabasal cell layers of the normal oral epithelium. In the oral squamous cell carcinoma, positive staining for p130 and Rb was observed in well-differentiated carcinomas (p130, 66.2%; Rb, 78.5%), more than in poorly differentiated ones (p130, 16.7%; Rb, 50.0%). In immunoelectron microscopic features, p130 protein was localized in the nucleus and mitochondria. The expression of p130 was related to the degree of tumor differentiation as that of Rb. It is suggested that p130 gene may be associated with the development of a wide variety of human malignancies rather than the progression.

Oral squamous cell carcinoma: electron microscopic and immunohistochemical characteristics

 Oral squamous cell carcinoma is the most common oral malignancy, and we performed electron microscopic and immunohistochemical investigation of the tumor. In patients with cervical metastasis, microvilli were developed and a small number of desmosomes were found, regardless of the width of the intercellular spaces. In patients without the metastasis, few microvilli were found in relatively wide intercellular spaces, or numerous microvilli were found in narrow intercellular spaces, and a large number of desmosomes were shown. However, these findings were different from those of tumors that had received radiotherapy, in which numerous microvilli and a small number of desmosomes were found in the nonmetastatic cases. Transferrin receptor, which is a marker of cell proliferation, was localized on the cell membrane, especially in microvilli. Ultrastructural similarity between the primary tumor and the metastatic tumor was recognized, however, the features of microvilli, desmosomes, and the intercellular spaces differed between them in most cases. It is suggested that microvilli might be related to the metastasis of oral squamous cell carcinoma cells. Immunohistochemically, the protein expression of p53 and pRb2/p130 was related to the clinical course of the patients with oral squamous cell carcinoma; the mechanism of the synthesis of these proteins should be investigated in order to understand the biological behavior of the tumor.

Malignant melanoma in the oral region: ultrastructural and immunohistochemical studies.

Malignant melanoma in the oral region is reviewed in its clinicopathological aspects. Clinically the melanomas were classified into five types; however, there were no histopathological differences according to these clinical types. Electron microscopic observation of the melanomas and primary culture cells derived from oral malignant melanoma revealed that, in patients whose prognoses were relatively good, many mature-stage melanosomes were found. Immunohistologically, there was a positive reaction for transferrin receptor and the expression of pRb2/p130 was found in only 2 of 13 patients, who are still alive after periods of over 14 years. The radiosensitivity of a cell line derived from human oral malignant melanoma was greater than that in cell lines derived from human cutaneous melanoma and with radiation, the number of melanosomes increased. There are very few clinical cases of oral malignant melanoma and very few cell lines derived from oral malignant melanoma, and so findings in these patients and these cell lines should be accumulated in order to clarify the biological behavior of oral malignant melanoma.

Mutation of p53 as a Prognostic Indicator in Patients with Oral Squamous Cell Carcinoma

Abstract Objective: The p53 gene is frequently mutated in patients with oral squamous cell carcinoma. However, the correlation between the mutation of the p53 gene and the prognosis for patients with oral squamous cell carcinoma is uncertain and this was investigated in this study. Patients and Methods: The correlation between the p53 mutation and the clinicopathological features of oral squamous cell carcinoma were examined. Samples were obtained from 81 patients with oral squamous cell carcinoma and the protein expression of p53 and the presence of mutation in exons 5 to 8 were investigated by immunohistochemistry and single-stranded conformation polymorphism, respectively. Results: Overexpression of p53 was found in 40 patients, and there was a correlation between its expression and the degree of differentiation, meaning that many p53 overexpressed tumours were poorly differentiated. However, there was no correlation between p53 expression and the 5-year cumulative survival rate. Mutation of p53 was recognised in 29 patients and the 5-year cumulative survival rate of patients with p53-mutated tumours was significantly lower than that of patients without p53 mutation. However there was no correlation between the presence of mutation and other clinicopathological features. Conclusion: From these results, it is suggested that p53 mutation may be a prognostic indicator for oral squamous cell carcinoma.

Postoperative Evaluation of Maxillofacial Deformity According to Facial Form Classification. Patients Evaluation by Questionnaire.

Data from questionnaires consisting of 36 items which were sent to patients with prognathism were analysed, for self-evaluation on the postoperative release from various troubles that were suffered before surgery.The subjects were 77 patients (14 males and 63 females) out of 147 patients who had undergone sagittal splitting ramus osteotomy in our clinic from 1989 to 1994. The patients were divided into three groups with different facial profile, skeleton, and occlusion: prognathism group (28 patients with mandibular prognathism only), asymmetry group (27 patients with mandibular prognathism with asymmetry), and open bite group (22 patients with mandibular prognathism and open bite).The results were as follows:1) As for the preoperative particular troubles, those concerning occlusion and facial profile were noted in the prognathism group and those concerning mastication in the open bite group. The patients in the asymmetry group had the same troubles as noted in the above two groups, but suffered from multiple troubles, including temporomandibular joint disorder and others. Moreover, they were comparatively younger.2) In the open bite group, only a few patients evaluated the postoperative change in the facial profile, but much more patients evaluated the change in speech after surgery.3) Over 90 per cent of the evaluated patients from the three groups the improvement of occlusion after the operation, but it took more time for patients to eat an ordinary meal satisfacorily in the asymmetry group.4) Preoperative discomforts due to the temporomandibular joint syndrome were most remarkable in the asymmetry group, but less reduced in the prognathism group after surgery.5) As for the change in tongue and the numbness of lip or chin after surgery, there were no significant differences among the three groups.6) The difference between before and after surgery in the open bite group was move noticeable than the others.7) As for the motive of undergoing surgery, although many patients were recommended to undergo surgery by dentists among the three groups, more patients from the prognathism group decided to undergo it by themselves.8) As for the overall evaluation for the result of surgery, most patients in the three groups showed positive response to surgery. As the main reason, aesthetic improvement was evaluated in the prognathism group, that of occlusion and mastication in the open bite group, and that of the psychological aspect in the asymmetory group.