Takashi Takasaki

Immunohistochemical studies on oncogene products (EGF-R, c-erbB-2) and growth factors (EGF, TGF-α) in human breast cancer: their relationship to oestrogen receptor status, histological grade, mitotic index and nodal status

In this investigation, 83 human mammary carcinomas were examined for the expression of oestrogen receptor (ER), epidermal growth factor receptor (EGF-R), epidermal growth factor (EGF), transforming growth factor alpha (TGF-α), c-erbB-2, histological grade, mitotic index and nodal status, all of which are reportedly prognostically significant factors (Bloom and Richardson 1957; Baak et al. 1985; Wright et al. 1989). ER expression was biochemically recognized in 43.4% of mammary carcinomas, and EGF-R, EGF, TGF-α and c-erbB-2 were histochemically recognized in 25.3, 14.5, 27.7 and 18.0% of mammary carcinomas examined respectively, using conventional sections of buffered formalin-fixed, paraffin-embedded tissue and monoclonal or polyclonal antibodies. There were significant relationships between negative ER and positive EGF-R or TGF-α; positive EGF-R and TGF-α; positive EGF-R and c-erbB-2; and positive c-erbB-2 and TGF-α. The single changes which were the negative ER and the positive c-erbB-2 correlated with histological grade and mitotic index. Co-expression of EGF-R and TGF-α correlated with positive nodal status. Therefore, the present investigation indicates that the negative ER, single expression of c-erbB-2 and co-expression of EGF-R and TGF-α are important markers which contribute indirectly to prognosis, which reconfirms previous findings on the former two while adding the new finding that immuno-histochemical demonstration of expression of EGF-R and TGF-α may provide useful information for selecting the appropriate treatment.

Expression of p53 protein in benign epithelial hyperplasia, atypical ductal hyperplasia, non-invasive and invasive mammary carcinoma: an immunohistochemical study.

To clarify whether p53 protein expression is involved in multistep carcinogenesis or the progression of mammary ductal carcinoma, we investigated p53 protein expression in 83 invasive ductal carcinomas (IDC), 10 IDC with a predominant intraductal component, 13 non-invasive ductal carcinoma (NIDC), 16 atypical ductal hyperplasia (ADH) and 39 benign epithelial hyperplasia (EH), using immunohistochemistry. Expression of p53 protein was detected in 24 (28.9%) cases of IDC, 5 (50%) cases of IDC with a predominant intraductal component and 1 (7.6%) case of NIDC. No expression was observed in either ADH or EH. In IDC, including cases with a predominant intraductal component, p53 protein expression was associated with a higher histological grade (P<0.0001) or mitotic index (P<0.0005). Although overexpression of c-erbB-2 protein has also shown a similar association with these prognostic indicators, expression of p53 protein correlated regardless of the status of c-erbB-2 overexpression. Completely coordinated expression of p53 protein was seen in both intraductal and invasive components. The intraductal component in IDC including cases with a predominant intraductal component which expresses p53 protein had significantly higher histological grade (P<0.0005) or more comedo-subtypes (P<0.0001). These results suggested that p53 protein expression occurs at a stage of NIDC with high histological grade or in comedo-subtypes. Its expression is maintained throughout invasion.

Apocrine Adenocarcinoma of the Bilateral Axillae

A case of apocrine adenocarcinoma arising in the bilateral axillae is reported. The patient was an 88 year old Japanese male who complained of a mass lesion and puslike discharge in the right axilla. Another mass was also noticed in the left axilla. No other neoplastic lesion was found in other sites of the body. The histologic appearances of the bilateral axillary tumors were almost identical. Both were adenocarcinoma with varying degrees of differentiation, composed of glands and nests of atypical epithelial cells with abundant eosinophilic cytoplasm. Some neoplastic cells exhibited cytoplasmic projections on their apical surface. Foci of in situ carcinoma were observed within the neoplastic tissue in the bilateral axillae. The neoplastic cells were immunohistochemically positive for epithelial membrane antigen (EMA) and gross cystic disease fluid protein (GCDFP‐15), but negative for carcinoembryonic antigen (CEA). On the basis of their histologic and immunohistochemical features and distinctive location, the tumors were diagnosed as apocrine adenocarcinoma. Acta Pathol Jpn 41: 927‐932, 1991.

Obesity affects expression of progesterone receptors and node metastasis of mammary carcinomas in postmenopausal women without a family history.

Possible relationships between risk factors, such as obesity and a family history of breast cancer, and prognostic factors of mammary carcinomas were investigated by examining the body mass index of patients and the expression of estrogen (ER) and progesterone receptors (PgR), c‐erbB‐2 and p53, grade of histology, size of tumors and nodal status of mammary carcinomas. There was no significant difference in the body mass index of premenopausal patients either with or without a family history. For postmenopausal patients, the body mass index was significantly low in patients with a family history compared with patients without a family history. In premenopausal patients with or without a family history and in postmenopausal patients with a family history, there was no significant difference in the body mass index regardless of the mammary carcinoma prognostic factor, such as expression of ER, PgR, c‐erbB‐2 and p53, grade of histology, size of tumors and nodal status. However, in postmenopausal patients without a family history, body mass index was significantly high for patients with mammary carcinomas that had PgR expression and node metastasis. These results suggest that obesity may affect the PgR status and nodal status of mammary carcinomas in postmenopausal patients without a family history.

The expression of thymidine phosphorylase/platelet‐derived endothelial cell growth factor is correlated to angiogenesis in breast cancer

It has been shown that human thymidine phosphorylase (TP) Is Identical to platelet‐derlved endothelial cell growth factor and has angiogenlc actlvhy. In the present study, the expression of TP was examined In 139 mammary carclnomas and 35 benign mammary disorders using biochemical and lmmunohlstochemlcal methods. Moreover, In order to evaluate the significance of TP expression in mammary carcinomas, the relationship between vascular density and various cllnicopathological factors, including age and menopausal status of patients with a mammary carcinoma, were compared wtth the size, nodal status, expression of estrogen receptor (ER), progesterone receptor (PgR), c‐erbB‐2, p53 and TP of a mammary carcinoma. Thymidine phosphorylase expression Increased in both the nuclei and cytoplasm of mammary carclnoma cells in comparison to mammary benign disorder cells. The number of mlcroves‐sels In mammary carcinomas was generally correlated to the number of tumor cells with TP expression in cytoplasm. The number of cells with TP expression in cytoplasm was significantly large In tumors that measured 34 cm In diameter, compared wtth tumors measuring 1–2 and 5–6 cm in diameter. In mammary tumors of 1–4 cm diameter, TP expression and vessel denslty were slgnlficantly high in tumors negative for ER or positive for cerbB2 and In tumors positive for TP or cerbB2, respectively; whereas tumors of 5–6 cm In diameter were not modified by any cllnlcopathological factors. The results lndlcated that TP plays an Important anglogenetic role In mammary carcinomas, especially tumors with a certain progression.

Immunohistochemical studies on expression of human vascular smooth muscle myosin heavy chain isoforms in normal mammary glands, benign mammary disorders and mammary carcinomas

The expression of myosin in normal and diseased mammary glands of 199 Japanese women was evaluated immuno‐histochemically by the avidin‐biotin peroxldase complex method using antibodies to three human smooth muscle myosin heavy chain isoforms derived from the vascular smooth muscle: myosin SM1 is expressed consistently from fetal stage to adulthood, myosin SM2 appears only in well‐differentiated smooth muscle after birth, and myosin SMemb is more abundant in embryonic aortas. SM1 was expressed in myoepithelial cells of normal mammary glands and fibrocystic diseases and in myoepithelial‐like tumor cells In the basal layer of fibroadenomas and phyllodes tumors. SM2 was expressed only In the myoeplthelial cells of mammary glands in breastfeeding women. SMemb was expressed more Intensely In the cytoplasm of luminal epithelial cells in larger fibroadenomas (P<0.01), or In the cytoplasm of carcinoma cells In lnvaslve ductal carcinomas with metastasized lymph nodes (P<0.001) and In those of higher histological grade (P<0.0001). Multivariate logistic analysis showed a significant correlation only between the expression of SMemb and histological grade (P<0.0001), which is a prognostic factor of mammary carcinomas. These findings suggested the possible prognostic value of SMemb.

Histological and biological characteristics of microinvasion in mammary carcinomas ≤ 2 cm in diameter

Fifty‐two mammary carcinomas, 2 cm or less in diameter, were examined in order to clarify the morphology and biology of microinvasion. The morphological characteristics of microinvasion of carcinomas include: (i) a loss of myoeplthelial cells and a rupture with concomitant loss of collagen IV and lamlnin in the basement membrane of involved mammary glands; and (ii) budding of carcinomas from the rupture into the stroma. When microinvasion was defined as a rupture of < 200 pm In the basement membrane with invasion, the number of microinvasions per 1 mm of basement membrane was larger in the tumors in which the area of invasion was larger. The prevalence of microinvasion showed a significant correlation with lymph node metastasis and the rate of histological deviation, while no correlation of expression of either estrogen receptors or progesterone receptors and c‐erbB‐2 protein was found. The study clarified that the early invasion of mammary carcinomas could be detected by the immunohistochemical method using anti‐smooth muscle actin, laminin and collagen IV antibodies. The study also suggested that microinvasion might be an indicator of lymph node metastasis in mammary carcinomas ≤ 2 cm diameter.

A Malignant Rhabdoid Tumor of the Kidney Occurring Concurrently with a Brain Tumor : Report of a Case

Malignant rhabdoid tumor of the kidney (MRTK) is one of the most lethal neoplasms to occur in young infants. Cases of MRTK accompanying an embryonal tumor in the central nervous system have occasionally been described. We present herein an interesting case of MRTK that was clinically diagnosed preoperatively. A male infant aged 6 months with both a midline brain tumor and a renal neoplasm was transferred to our institution. Although roentgenographic evaluation suggested that the renal lesion was a Wilms’ tumor, midkine (MK), a growth and differentiation factor characteristically present in the urine of patients with Wilms’ tumor, was not detected. A preoperative diagnosis of MRTK was established based on the lack of urinary MK in addition to the typical clinical features of the young age and the concurrent brain tumor.

Sharp increase in the incidence of mammary Carcinoma in Kagoshima prefecture, Japan

Between 1986 and 1990, among a female population of about 0.95 million, 1184 women living in Kagoshima Prefecture were diagnosed pathologically as having mammary carcinoma. The number of patients with mammary carcinoma, the crude incidence rate per 100 000 women and age-standardized mammary carcinoma incidence rates were 205, 21.29 and 19.42 in 1986, 212, 22.04 and 19.48 in 1987, 238, 24.74 and 21.8 in 1988, 245, 25.47 and 22.33 in 1989 and 284, 29.57 and 25.69 in 1990, respectively. The number of patients with this disease increased annually. The increase in the age-specific incidence rate of this type of cancer between 1986 and 1990 was 1.38-fold in women between 40 and 49 years of age, 1.46-fold in women between 50 and 59, 1.37-fold in the 60–69 age group, 1.48-fold in the 70–79 age group and 1.91-fold in women over 80. In both the urban and rural areas, the incidence increased annually during the course of this study. In 1990, the age-standardized mammary carcinoma incidence rate in urban area was 1.17 times that in rural area.