Yukiyoshi Esaki

Osteopontin mRNA is expressed by smooth muscle-derived foam cells in human atherosclerotic lesions of the aorta.

Osteopontin is a phosphorylated, sialic acid-rich, noncollagenous bone matrix protein containing the Arg-Gly-Asp-Ser amino acid sequence responsible for cell adhesion. The protein strongly binds to hydroxyapatite and play an important role in calcification. Expression of osteopontin mRNA was analyzed in human aortic atherosclerotic lesion by Northern blot hybridization, as well as by in situ hybridization. The expression of osteopontin mRNA was detected in 24 out of 25 samples of aorta obtained from 17 autopsy cases, but not in one normal aortic sample. The magnitude of expression was proportional to the stage of atherosclerosis. In situ hybridization revealed that the cells expressing osteopontin mRNA were detected in the wall surrounding atheroma and closely associated with calcification. They were morphologically identified as foam cells and immunohistologically positive with HHF35, appearing to be derived from smooth muscle cells. These findings have suggested that smooth muscle cell-derived foam cells express osteopontin mRNA and play an important role in calcification of the atherosclerotic lesions.

Age-related mitochondrial DNA deletion in human heart: Its relationship with cardiovascular diseases

Background and aims: Accumulation of damage to mitochondrial DNA (mtDNA) occurs in myocardial tissue with advancing age. However, despite higher incidence of cardiac diseases in the elderly, little attempt has been made to detect deletions of mtDNA in the myocardial tissue of aged individuals. The aim of the present study was to clarify the relationship between aging, mtDNA deletion and cardiovascular (CV) diseases. Methods: We examined 163 autopsy cases, aged 60 years or older, using two different kinds of polymerase chain reaction (PCR): highly sensitive PCR to detect a common 4977- bp deletion and long- PCR for multiple deletions, which could be detected in case that deleted mtDNA accounted for more than several percents in total mtDNA. Results: The common 4977- bp deletion was detected in 156 cases (95.7%), showing no significant difference among these age groups and no relation to CV diseases. By long- PCR, multiple deletions in cardiac mtDNA were found in 33 (20.2%) of 163 cases. The proportion of the mtDNA deletion in the nineties (46.2%) was significantly higher than those in the younger (15.3%, p<0.05). Female predominance was significantly found in the group with the mtDNA deletion (p<0.05). Multiple deletions of mtDNA were not significantly related to ischemic change, valvular diseases, left ventricular hypertrophy, congestive heart failure, coronary sclerosis, or heart weight except for right ventricular hypertrophy. Conclusions: These findings suggest that there is a close relationship between aging and deletion of mtDNA, and that the ratio of deleted mtDNA to total mtDNA increases with advancing age. Age-related deletion of mtDNA may have little influence on CV diseases except for right ventricular hypertrophy.

A comparison of patterns of metastasis in gastric cancer by histologic type and age

Patterns of metastasis were examined in 173 autopsy cases of gastric cancer in which the primary tumor had not been resected and the death was mainly caused by growth and metastasis of the cancer. The results were compared by different histologic types as well as different age groups. From the histologic viewpoint, gastric cancer of glandular type showed preferential metastasis to the liver, whereas the nonglandular type showed a preference for peritoneal involvement and lymph node metastasis. With regard to age, peritoneal involvement was more frequently observed in younger patients for both glandular and nonglandular types. Younger patients also had a higher incidence of lymph node metastasis of gastric cancer of nonglandular type, but not for the glandular type. Regarding liver metastasis, there was no difference in incidence between different age groups.

Multiple gastric cancers in the aged with special reference to intramucosal cancers

A histopathologic study was made on 512 specimens of gastric cancer that were surgically obtained from aged patients (mean age 73 years) in the Tokyo Metropolitan Geriatric Hospital. Of the 512 cases studied, 408 were gastric cancer of the glandular type (80%) and 104 were of the nonglandular type (20%). There were 75 cases of gastric cancer consisting of multiple independent cancer lesions and 71 of these were histologically diagnosed as multiple (2–5) gastric cancers composed of glandular type only. Of these 71 cases, 21 cases were multiple intramucosal cancers. These 21 cases of multiple intramucosal cancers were compared with 49 cases of single intramucosal cancers of glandular type in terms of the maximum diameter of each lesion and the location within the stomach. The results suggest that, in aged patients, there is a great possibility that collision of multuple cancer lesions may result in a single intramucosal gastric cancer measuring over 3 cm in diameter.

Correlation of telomere lengths in normal and cancers tissue in the large bowel.

The hypothesis that telomeres in colorectal cancer cells exhibit age-related shortening, as in normal cells of the colorectal epithelium, was tested with samples of non-cancerous mucosa and cancer tissue from 124 patients (aged 29-97 years). Shortening with aging could be demonstrated for both normal and cancer tissues; regression analysis showed rates for length reduction of 44 and 50 base pair/year, respectively. Straight, essentially parallel, lines were obtained for the two cases, normal tissue values being about 2 kilobase pairs (kbp) higher, with a significant correlation between data at the individual patient level.

Pathologic characteristics of gastric cancer in the elderly: a retrospective study of 994 surgical patients

BackgroundThe clinicopathologic features of gastric carcinoma in elderly people have been reported previously. The present study examined the patterns and distribution of gastric carcinomas in the elderly, especially in patients aged 85 and older.MethodsA retrospective study of 994 consecutive Japanese patients aged 65 years or older was performed. In this group, a total of 1147 lesions were analyzed. Pathological findings in the very old group (older than 85 years; n = 126) were compared with those in younger groups (65–74 years [young-old group]; n = 356) and (75–84 years [middle-old group]; n = 512).ResultsWhile the male-to-female ratio significantly decreased with advancing age, the relative odds of gastric cancer in men were higher than those in women in all age groups. In the very old group, cancer of the lower third of the stomach tended to increase with advancing age, and accounted for 43.7% of cases. In the population overall, differentiated-type adenocarcinoma accounted for 89.6% in the early cancers and 50.3% in the advanced cancers. The proportion of cases involving differentiated-type carcinoma significantly increased with advancing age in early cancer and female advanced cancer cases, whereas no significant change was found in male advanced-cancer patients. In the very old group, lymph node metastasis was found in 5.4% of early cancers and 72.7% in advanced cancers. Multiple cancers significantly increased with advancing age (P < 0.05; 10.7% in the younger-old group, 12.7% in the middle-old group, and 19.0% in the very old group).ConclusionThese results indicate that, in the very old group, gastric cancers showed a distal shift with predominantly differentiated-type carcinoma in the early stages and increased undifferentiated-type carcinomas in advanced stages. These results suggest increased histologic diversity with tumor growth. These findings have important implications for the screening and diagnosis of gastric cancer in the elderly.

Breast carcinoma in women over the age of 85: distinct histological pattern and androgen, oestrogen, and progesterone receptor status

Aims:  The pathogenesis of breast carcinoma in very elderly women is of interest, because oestrogen levels are likely to be extremely low during the development of the disease. In an effort to understand the pathogenesis of breast carcinoma in these women, this study was undertaken to compare the histological patterns and hormone receptor status of breast carcinomas arising in very elderly and younger women.

Histologic and biologic patterns of microscopic pancreatic ductal adenocarcinomas detected incidentally at autopsy

The major clinical problems with pancreatic carcinoma are its silent course and late, fatal clinical manifestation. The results of treatments of small pancreatic carcinomas (<2 cm in greatest dimension) have led to the assumption that the detection of these cancers at earlier stages would lead to better survival and possible cure. Currently, there is no information about the histologic and biologic patterns of early stage pancreatic carcinoma, and the available data on incidentally detected tumors are fragmentary. The authors observed two incidental microscopic pancreatic ductal adenocarcinomas in female patients who died of advanced gastric carcinoma (Case 1) and renal carcinoma (Case 2).

Telomere shortening in gastric carcinoma with aging despite telomerase activation

Abstract In the present study, we analyzed both telomere length and telomerase activity in surgical and autopsy samples of non-neoplastic mucosa and carcinomas of the stomach. Telomere length, determined by Southern blot analysis, demonstrated progressive shortening with age in non-neoplastic gastric mucosal specimens from 38 human subjects aged between 0 and 99 years, with an average annual loss rate of 46 base pairs (bp). The mean (±SD) telomere length in 21 gastric carcinomas was 7.0 ± 1.6 × 103 base pairs (1.6 kbp). In 20 (95%) of the 21 subjects, the values were smaller than those in the non-neoplastic gastric mucosa (mean shortening 1.8 kbp), although a strong correlation was observed for the paired data (r = 0.69, P = 0.0004). Similarly, telomere lengths in carcinomas were shorter than those for intestinal metaplasia (a mean difference of 1.1 kbp). Telomerase activity, estimated using the telomeric repeat amplification protocol assay, was positive in 18 (86%) of the 21 gastric carcinomas, without significant differences among the three histological types (well, moderately, and poorly differentiated adenocarcinomas) or with sex or age. The results suggest that telomere length and possibly shortening rates vary with the individual, and that examination of both non-neoplastic mucosa and tumors is necessary to improve our understanding of the significance of telomerase in neoplasia.

Oncocytic Adenocarcinoma of the Stomach: Parietal Cell Carcinoma

We report 10 cases of an unusual type of gastric adenocarcinoma that occurred in elderly patients 58–81 years of age. Histologically, the tumors were well to moderately differentiated tubular adenocarcinomas with very eosinophilic, finely granular cytoplasm. Immunohistochemical stains for antimitochondrial antibody were strongly positive. Ultrastructurally, the tumor cells had numerous mitochondria in their cytoplasm and occasional intracytoplasmic lumina with associated long microvilli. These histologic and ultrastructural features are similar to those of parietal cells in normal gastric fundic mucosa, but immunohistochemical staining of the tumors using four different antiparietal cell antibodies (anti-H+-K+-adenosine triphosphatase antibodies) was negative in all cases. Therefore, we think that these tumors were not parietal cell carcinomas but could be termed oncocytic adenocarcinomas, or adenocarcinomas with oncocytic differentiation. Previously reported cases of parietal cell carcinoma have been said to have a favorable prognosis, but it will be necessary to study a larger number of cases to determine the prognosis of oncocytic adenocarcinoma.