Gen Matsunaga

Aromatase in Human Bone Tissue

Peripheral aromatization of androgens exert estrogenic actions in many tissues. Recently in situ production of estrogens by aromatase was detected in human bone and cultured osteoblasts and has been proposed to participate in the maintenance of bone mass. We examined aromatase expression by immunohistochemistry and mRNA in situ hybridization in 16 cases of tibia (female 2 male, 14 female, 62 ± 5.2 years old) and quantified the level of aromatase mRNA in 28 cases of rib, femur, and lumbar vertebrae (16 male, 12 female, 58.0 ± 11.3 years old) by reverse transcriptase‐polymerase chain reaction (RT‐PCR) in order to study whether or not and in which cell types aromatase was expressed in human bone tissues. We also studied alternative use of multiple exons 1 of its gene and immunolocalization of type I 17β‐hydroxysteroid dehydrogenase (HSD), which converts estrone produced by aromatase to estradiol. Strong aromatase immunoreactivity and mRNA hybridization as well as type I 17β‐HSD immunoreactivity were detected in lining cells, osteoblasts, chondrocytes of articular cartilage, and adipocytes adjacent to bone trabeculae in all the cases examined. Amounts of aromatase mRNA varied greatly among the subjects (11.25 ± 9.77, 0.61–42.84 attomol/ng of total RNA). The amount of aromatase expression was not correlated with age or gender of the subjects but positively correlated with the degree of osteroporotic changes evaluated by radiological findings of lumbar vertebrae. Analysis of multiple exons 1 revealed that 1b or fibroblast type was predominantly (23/26) utilized as a promoter of aromatase gene expression. These results demonstrated that aromatase is expressed widely in human bone tissue and may play important roles in maintenance of human bone tissue.

Correlations between p21 expression and clincopathological finding, p53 gene and protein alteration, and survival in patients with endometrial carcinoma

The p21 protein inhibits cyclin‐dependent kinases and mediates cell‐cycle arrest and cell differentiation. It is induced by wild‐type p53, but not by mutant p53. This study of 75 patients with endometrial carcinoma investigates the relationship between p21 expression and the functional status of p53, and the usefulness of p21 as a prognostic marker. Correlations were determined between p21 immunoreactivity, p53 overexpression as examined by immunohistochemistry, p53 DNA mutations as examined by polymerase chain reaction–single‐stranded conformation polymorphism (PCR–SSCP) analysis, and clinicopathological features, including the clinical outcome. Immunoreactivity for p21 and p53 and p53 mutations were detected in 47 (62·7 per cent), 37 (49 per cent), and 23 (31 per cent) patients, respectively. There were no significant correlations between the presence or absence of p21 immunoreactivity and p53 overexpression and DNA mutations. Survival curves revealed that patients with p53 overexpression tended to have a poorer prognosis than those without p53 overexpression (P=0·104), that patients with p53 mutations had a significantly worse prognosis than those without mutations (P=0·035), and that patients with p21 expression tended to have a better prognosis than those without p21 expression (P=0·074). Immunohistochemical analysis of p21 was not useful for evaluating the functional status of p53 in patients with endometrial carcinoma. Both p21 expression and p53 abnormalities were considered as prognostic indicators in patients with endometrioid endometrial carcinoma.

Prognostic value of epidermal growth factor receptor expression in endometrioid endometrial carcinoma

We report here a retrospective study of epidermal growth factor receptor (EGFR) expression in 140 patients with human endometrioid endometrial carcinoma (median period of follow-up, 43.8 months; ranging from 1 to 155 months). Tumor specimens were immunohistochemically examined for the overexpression of EGFR, and the correlation among EGFR status, various clinicopathologic parameters, and prognosis was statistically evaluated. Monoclonal antibody (clone 31 G 7), which recognizes the extracellular domain of the EGFR molecule, was used for immunostaining. Ninety-four of 140 cases were immunohistochemically positive for EGFR (67.1%). The presence or absence of EGFR did not correlate with surgical stage, depth of myometrial invasion (DI), or lymph node involvement, but did correlate with histological grade and patients age. Furthermore, patients with EGFR-positive endometrial carcinoma had a statistically significant shorter length of survival than those with EGFR-negative tumors (P = .018). This trend is more apparent among the patients more than 50 years old (P = .003). When adjusted for surgical stage, DI, and patient age, EGFR status retained prognostic value by multivariate analysis. However, when adjusted for surgical stage, histological grade, DI, and patient age, EGFR status failed to retain prognostic value by multivariate analysis. The results of this study suggest that EGFR expression is correlated with histological grade and greater invasiveness of human endometrioid endometrial carcinoma.

Mass screening for cancer of the uterine cervix in Miyagi Prefecture, Japan : Effects and problems

OBJECTIVE To evaluate the effects of and problems with mass screening and in Miyagi Prefecture, Japan. STUDY DESIGN About 3,570,000 females who underwent mass screening for cervical cancer between 1962 and 1994. RESULTS The screening rate in the female population aged 30 years or older was 9.5% in 1970, gradually increased and exceeded that rate in 1991 but showed only slight changes thereafter. The standardized death rate due to malignant neoplasm of the cervix fell from 12.1 per 100,000 in 1961 to 4.0 in 1994. CONCLUSION There still remain various problems, such as lack of a further increase in the screening rate, the fixation of examinees and an increase in the incidence of cervical cancer in young females.

Mass Screening for Cancer of the Endometrium in Miyagi Prefecture, Japan

OBJECTIVE To survey the results of mass screening for cancer of the endometrium performed over a six-year period in Miyagi Prefecture, Japan. STUDY DESIGN Materials were cytodiagnostic samples of the endometrium examined by the Miyagi Cancer Society. The samples were classified into two groups: The mass screening group, from whom samples were collected according to the Health and Medical Service Law for the Aged, and the outpatient group, consisting of samples from other patients. The rates of subjects judged to require close examination and the detection rate of cancer of the endometrium in the two groups were compared. RESULTS In the mass screening group, the rate of subjects judged to require close examination and the detection rate of cancer of the endometrium were 2.3% and 0.11%, respectively, while they were 5.9% and 0.39%, respectively, in the outpatient group; the differences between the two groups were significant. CONCLUSION To improve the detection rate in mass screening for endometrial cancer according to the Health and Medical Service Law for the Aged, it is necessary to establish a new criterion for selecting subjects.

Glandular atypical cells in cervical smears after conization

目的:子宮頸部円錐切除後にみられた頸管腺異型細胞の特徴と臨床的意義について検討した.方法:対象は1994～2000年に子宮頸部円錐切除術を施行した43例である. 術後経過観察中に子宮腟部スパーテル擦過および頸管ブラシで採取した標本で, 頸管腺異型細胞の有無とその異型像, 出現時期および上皮内腺癌との鑑別等を調べた.成績:術後の頸管腺異型細胞は高頻度で認め, 出現は一過性より持続性が多かつた. 標本背景は清, 出現形式は柵状とシート状が大部分で, 柵状集塊の核には重積性や配列の乱れが認められた.胞体はライトグリーン好性, 核形は楕円形で核縁肥厚はなかった. 核過染性は軽度から中等度, クロマチンは細網状, 細顆粒状で均等に分布していた. 症例の44%に子宮内膜の腺細胞や間質細胞が認められた.結論:子宮頸部円錐切除後の頸管腺異型細胞は腺異形成や卵管上皮化生, 再生上皮に類似し, AGUS (atypical glandular cells of undetermined significance) の範疇に属すると考えた. 細胞集塊の形状では, 上皮内腺癌と鑑別困難なものもあるが, 上皮内腺癌でみられる核腫大や粗クロマチン, 核縁肥厚, 核分裂像はなく, 細胞異型により両者の鑑別は可能であった. 子宮内膜細胞の存在はこれらの診断の手助けとなった.