Frequent loss of heterozygosity but rare microsatellite instability in oesophageal cancer in Japanese and Chinese patients.

Reported frequencies for microsatellite instability (MSI) in oesophageal cancer differ widely in the literature, perhaps due to the high incidence of loss of heterozygosity (LOH) in this cancer. Using high-resolution fluorescent microsatellite analysis (HRFMA), we analysed microsatellite alterations in detail in 50 Japanese and 50 Chinese patients with squamous cell carcinoma in the oesophagus. In HRFMA, several devices have been developed to improve the detection characteristics, reproducibility of polymerase chain reaction and the migration accuracy of electrophoresis. All the alterations observed were separable into MSI, LOH and alterations ambiguous for both. MSI was rare in these panels of oesophageal carcinomas. The frequencies of MSI in the Japanese and Chinese subjects were 8 and 4%, respectively. All the alterations were mild (within 2 base pairs) and were observed in a limited number of markers. More drastic types of MSI, such as those typical in colorectal cancer, were not observed. On the other hand, the incidence of LOH was high, reaching 50% for the Japanese and 70% for the Chinese subjects. In many of these cases, LOH was observed in multiple microsatellite markers. The frequency of LOH in each marker was not apparently biased. Although in many cases MSI and LOH were clearly distinguished with use of the sensitive and quantitative fluorescent assay, theoretically indistinguishable patterns were noted in some cases. In conclusion, MSI is rare and LOH predominates in squamous cell carcinoma in the oesophagus.

Risk factors for multicentric occurrence of carcinoma in the upper aerodigestive tract-analysis with a serial histologic evaluation of the whole resected-esophagus including carcinoma.

BACKGROUND AND OBJECTIVES: We have reported that both lifestyle and family history might be related to multiplicity of carcinoma in the upper aerodigestive tract (UADT). The aim of this study was to elucidate the relationship between the number of carcinomas and risk factors. METHODS: A serial histologic evaluation of the entire non-irradiated esophagus was performed in 114 males with esophageal cancer who were divided into three groups (group I: 88 cases with solitary cancer, group II: 11 with double cancers, group III: 15 with three or more cancers). As controls, 228 males with benign diseases were selected. RESULTS: Among group III patients, both the incidence of heavy smoking and that of heavy drinking were 67% and 60%, which were significantly higher than those of group I (28% and 30%) and control subjects (14% and 10%, respectively). Heavy drinkers who were also heavy smokers were observed in 2, 10, 27, and 47% in control subjects, groups I, II, and III, respectively. Regarding family history, 27% of group III had a close relative with UADT or lung cancer, while the incidence was 7% in the control. CONCLUSIONS: These findings strongly support the hypothesis that heavy smoking and heavy drinking, as well as a family history of both UADT and lung cancer, might be risk factors for multicentric occurrence of UADT cancer.

Pathologic features of superficial esophageal squamous cell carcinoma with lymph node and distal metastasis.

BACKGROUND: Endoscopic mucosal resection (EMR) is a less invasive localized treatment for patients with esophageal carcinoma. However, indications for EMR use in cases of superficial esophageal carcinoma are controversial. The authors evaluated histopathologic risk factors for lymph node metastasis and recurrence. METHODS: In the specimens resected, the authors examined depth, the superficial area and the area attached to or infiltrating the lamina muscularis mucosa. RESULTS: The authors found that the superficial area and the attached or infiltrated area reflected the depth of the tumor. However, there was a recurrence of esophageal carcinoma even in m3 cases attached only to the lamina muscularis mucosa. CONCLUSIONS: The authors concluded that ml and m2 esophageal carcinoma had almost no risk of lymph node metastasis and recurrence no matter how extensive the superficial area. In addition, sm2 and sm3 carcinoma have a high frequency of lymph node metastasis and recurrence. M3 and sm1 carcinoma run the risk of lymph node metastasis and recurrence however small the superficial area and the area attached to or infiltrating the lamina muscularis mucosa. Treatment strategies for patients with superficial esophageal carcinoma, including EMR, should take the above findings into account.

p53 protein accumulation in multiple oesophageal squamous cell carcinoma: relationship to risk factors.

To clarify mechanisms involved in the carcinogenesis of multiple oesophageal squamous cell carcinoma, the expression of p53 protein in 46 lesions surgically excised from 13 Japanese patients was investigated immunohistochemically and the relation of p53 protein accumulation to the patient's history of alcohol consumption and cigarette smoking was analyzed. p53 protein accumulation was observed in 13 main lesions, that is in 6 (85.7%) of 7 subjects with a history of heavy drinking and smoking, but only in 1 (16.7%) of 6 with no such history (Fisher's exact test, p = 0.025). As regards the 46 lesions, p53 protein accumulation was evident in 22 (88.0%) of 25 lesions of the high-risk patients, but in 7 (33.3%) of 21 lesions of the other subjects (Fisher's exact test, p < 0.001). p53 protein accumulation was similarly recognized in all oesophageal lesions in 5 of 7 high-risk patients. Thus, use of both alcohol and cigarettes is clearly associated with a high frequency of p53 protein accumulation in multiple oesophageal squamous cell carcinoma present at the same time. These findings are considered to support the concept of field carcinogenesis of the oesophagus.