Yasumasa Hirano

p53 gene mutations in oral carcinomas from India

In this study, we analyzed 53 oral squamous‐cell carcinomas among Indians for the presence of alterations in the tumor‐suppressor gene p53 by PCR‐SSCP and sequencing methods. Our results showed that 21% (II/53) of oral carcinomas analyzed carried mutations within the exons 5–8 of the p53 gene. We have identified II single‐base pair substitutions consisting of 10 mis‐sense mutations and one at the splice acceptor site, and one deletion mutation involving 4 consecutive bases. The majority of the base substitutions were transitions (5 TA to CG and 5 GC to AT), while only one transversion (TA to GC) was observed. Probable hot‐spots for the mutation induction were identified at codons 149 and 274, which have not been observed before in head‐and‐neck cancers. The mutational spectrum might have originated from base alkylations at guanine and thymine residues, caused by some alkylating agents. The present results are thus consistent with the involvement of tobacco‐related nitrosoamines in the etiology of oral squamous‐cell carcinoma.

Detection of p53 Gene Mutations in Human Ovarian and Endometrial Cancers by Polymerase Chain Reaction‐Single Strand Conformation Polymorphism Analysis

The presence of mutations in the p53 gene was examined in ovarian cancers by a polymerase chain reaction‐single strand conformation polymorphism (PCR‐SSCP) analysis. The primers were designed to amplify exons 5 through 9 that contain phylogenetically conserved domains of the p53 gene. Mutations were detected in 5 out of 10 cases, one of which contained a deletion in the second allele. A single base substitution was detected in 4 cases at codons 162,175, 205 and 273 and a single base insertion in one case within codon 315. A high frequency of p53 mutations in ovarian cancers and lack of mutation in 6 benign ovarian tumors and 2 normal ovaries suggested that the mutation of the p53 gene was associated with the genesis and/or progression of ovarian cancer. In 1 of 7 endometrial cancers, two mutations at codons 239 and 254 were detected.

Pathologic and imaging findings of an oncocytoma in the deep lobe of the left parotid gland.

Oncocytoma is a rare salivary gland tumour consisting of oncocytes with many hyperplastic mitochondria. It usually occurs in the parotid gland. Because the features of oncocytoma resemble those of other benign and low-grade-malignant salivary gland tumours, clinical diagnosis is often challenging. This report presents the pathologic and imaging findings of an oncocytoma arising in the deep lobe of the left parotid gland in a 66-year-old man. Oncocytoma was diagnosed on the basis of histological, magnetic resonance imaging, and scintigraphic findings. The tumour showed accumulation of technetium-99m pertechnetate and decreased signal intensity on both T1- and T2-weighted magnetic resonance images.

The Abnormal Expression of p53 Protein is a Predictive Prognostic Marker in Oral Leukoplakia

Abstract Objectives: The p53 tumour suppresser gene has been studied as a prognostic marker of oral squamous cell carcinoma. This study was conducted to search for a p53 predictive prognostic marker in oral premalignant leukoplakia using p53 immunostaining. Patients and Methods: Oral leukoplakia with epithelial dysplasia (60 patients) and healthy oral mucosa (15 patients) were immunohistochemically stained for the p53 protein. The healthy oral mucosa were obtained from a separate group of patients. Results: Fifty percent of the leukoplakia lesions were positive for p53 protein. Among the 60 lesions, 13 developed into squamous cell carcinoma, of which 10 showed p53 positive staining even before malignant transformation. Conclusion: Overexpression of p53 protein may be a useful diagnostic procedure for oral leukoplakias that have a high probability of developing into oral squamous cell carcinoma.

The Effect of Recombinant CD80-Adenovirus and Interleukin-12 on Generation of Cytotoxic T Lymphocytes Against Autologous Tumour in Patients with Oral Squamous Cell Carcinoma

Abstract Objectives: The combined effect of a costimulatory molecule, CD80 and interleukin-12, on generation of cytotoxic T lymphocytes against autologous tumour cells was investigated using peripheral blood lymphocytes from patients with oral squamous cell carcinoma. Materials and Methods: The use of recombinant adenovirus enabled efficient transduction of CD80 into all primary cultured squamous cell carcinoma cells. Peripheral blood mononuclear lymphocytes from patients with oral squamous cell carcinoma were co-cultured with CD80-transduced autologous tumour cells in the presence of interleukin-12. Results: The levels of cytotoxicity against autologous tumour in patients with squamous cell carcinoma were individually variable. However, the cytotoxicity against autologous tumour cells, but not against allogeneic tumour cells, was efficiently inhibited by the addition of either anti-CD3, anti-CD8, or anti-MHC class I mAb, suggesting that the induced cytotoxicity was specific for autologous tumour cells. Conclusion: The results suggest that generation of tumour-specific cytotoxic T lymphocytes using a combination with CD80 costimulation and interleukin-12 is effective in oral squamous cell carcinoma patients. However, a further approach for expanding the number of specific effector cells will be required for clinical application.

Immunohistochemical analysis of the p53 tumor suppressor gene product in oral leukoplakia

Squamous Cell Carcinoma (SCC) is the most frequent malignancy in the oral cavity. p53 protein has been reported to be expressed at high levels in malignant lesions, while the level in premalignant lesions has yet to be determined. In this study, oral leukoplakia and oral SCC were examined. Seventy-four incision or excision samples from 43 cases diagnosed as leukoplakia, and 41 samples from 37 SCC cases in the oral cavity, were obtained. All samples (formalin-fixed, paraffin embedded) were examined immunohistochemically for overexpression of p53 protein with monoclonal antibody BP 53-12. As the result, 1. Twenty-two out of 43 leukoplakia cases, and 29 out of 37 oral SCC cases, were positive for p53 protein. 2. p53 protein was overexpressed in premalignant lesions, especially in the cases with moderate and severe epithelial dysplasia. 3. There was a relation between p53 protein expression and pathological features of leukoplakia (epithelial dysplasia), statistically. 4. There was a relation between p53 protein expression and clinical features of leukoplakia, statistically. 5. Malignant transformation during clinical observation was seen in 11 cases. Nine out of 11 cases were positive for p53 even before malignant transformation. Since in cancer-development cases, p53 staining was detected even before malignant transformation of oral leukoplakia to squamous cell carcinoma, it is indicated that p53 accumulation occurred at a early stage of cancer-development. In conclusion, immunohistochemical analysis of p53 protein is suggested to be useful diagnostic procedure for oral leukoplakia, which may develop into oral SCC.