Ikuo Matsuyama

Involvement of vascular endothelial growth factor and urokinase-type plasminogen activator receptor in microvessel invasion in human colorectal cancers.

To evaluate the association among known angiogenic growth factors or factors related to the plasminogen activation system and clinicopathological factors in patients with colorectal cancer, we examined the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor‐α (TGF‐α), urokinase‐type plasminogen activator (u‐PA), u‐PA receptor (u‐PA‐R) and plasminogen activator inhibitor‐1 (PAI‐1) in clinical specimens of colorectal cancers by Northern blot analysis. In comparison with the expression of these angiogenesis‐related genes in 7 paired samples of colorectal cancers and the adjacent normal mucosa, VEGF mRNA level was significantly higher in the cancer tissues than in the adjacent normal mucosa (p < 0.05). We analyzed expression of these genes in 44 cases of primary colorectal cancers. Among the 3 angiogenic growth factors we examined, VEGF mRNA expression was significantly higher in the cancer tissues with blood vessel invasion or with lymphatic vessel invasion than in those without, respectively (p < 0.05). On the other hand, u‐PA‐R mRNA expression was significantly higher in the cancers with blood vessel invasion than in those without (p < 0.05). In addition, there was a correlation between the expression levels of VEGF and u‐PA‐R mRNA in the cancer tissues we have examined. Using immunohistochemistry, strong staining of VEGF or u‐PA‐R was observed in the cancer cells invading the microvessels. Our findings suggest that malignant transformation might accompany the upregulation of VEGF expression in colorectal cancers and that VEGF and u‐PA‐R might contribute cooperatively to increase angiogenesis around the tumor as well as the metastasis via microvessels. Int. J. Cancer (Pred. Oncol.) 79:179–186, 1998.© 1998 Wiley‐Liss, Inc.

Clinicopathological characteristics of atypical cystic duct (ACD) of the breast: Assessment of ACD as a precancerous lesion

To clarify the clinicopathological features of an atypical cystic duct (ACD) as defined by Tsuchiya’s criteria as a precancerous lesion of the breast, we used 200 whole mammary gland serial sections of breast cancer. Forty‐four (22%) of the 200 breast cancer patients had ACD breast lesions. The frequency of patients with ACD increased in premenopausal women (P= 0.001). There was no correlation between the ACD‐present group and the ACD‐absent group for immunohistochemical status of the estrogen receptor (ER), progesterone receptor (PgR), p53, or c‐erbB2; Ki‐67 labeling index of cancer tissues; size of tumor, or lymph node metastases. A number of ACD lesions displayed continuity to cancer lesions. In 500 serial sections of a paraffin‐embedded tissue of a ACD case at 3 μm intervals, an apparent transition from ACD into ductal carcinoma in situ was observed. Immunohistochemical analysis using α‐smooth muscle actin showed that myoepithelial cells of ACD stained strongly, and their nuclei and cytoplasm were thinning. In 16 of the 44 (36%) ACD‐present patients, carcinoma cells stained positive for p53. Within those 16 cases, 12 cases (75%) were positive for p53 in ACD lesions. There was a significant correlation between the expression of p53 protein in malignant cells and ACD (P= 0.001). All 44 ACD lesions had no staining of c‐erbB2, regardless of staining in malignant lesions. The mean Ki‐67 labeling index of ACD lesions was low (0.3%), suggesting that ACD had a low proliferative rate. We suggest that ACD is the precancerous breast lesion because of a histologic continuum between ACD and malignancy, and because of p53 protein expression in ACD.

Clinicopathologic features and incidence of invasive lobular carcinoma in Japanese women

Intending to clarify the true Incidence of Invasive lobular carcinoma of the breast In Japanese women as well as the frequency of unilateral multlcentriclty, 362 cases of clinically defined monocentrlc breast cancer without pre‐operative biopsy (previously fine needle aspiration or needle biopsy were routinely carried out for every case) were examined by whole mammary gland serial sectioning. On the basis of pathology and the World Health Organization classification of breast tumors, each case was assigned to one of two main histologlc types: Invasive lobular carcinoma (ILC) or Invasive ductal carcinoma (IDC). Invasive lobular carcinoma was further separated into classic and variant types by employing previously published criteria. Twenty‐one cases of ILC (5.8%) were diagnosed, which Is more than In most previous Japanese studies. Unilateral multicentric breast carcinoma was detected In 9.5% of ILC and 16.1% of IDC (the difference was found not significant). Microscopically, ILC tumors were found to be, on average, larger than IDC. Patients with classic type ILC tended to be younger than those with variant type or IDC. Estrogen receptor expression was found more frequently In variant type ILC than in classic type. These results suggest that the incidence of invasive lobular carcinoma of the breast In Japanese women is low and that unilateral multicentricity Is not significantly higher in ILC than in IDC.

Extrahepatic expression of apolipoprotein A-II in mouse tissues: Possible contribution to mouse senile amyloidosis

Apolipoprotein A-II (apoA-II), an apolipoprotein in serum high-density lipoprotein, is a precursor of mouse senile amyloid fibrils. The liver has been considered to be the primary site of synthesis. However, we performed nonradioactive in situ hybridization analysis in tissue sections from young and old amyloidogenic (R1.P1-Apoa2 c ) and amyloid-resistant (SAMR1) mice and revealed that other tissues in addition to the liver synthesize apoA-II. We found a strong hybridization signal in the basal cells of the squamous epithelium and the chief cells of the fundic gland in the stomach, the crypt cells and a small portion of the absorptive epithelial cells in the small intestine, the basal cells of the tongue mucosa, and the basal cells of the epidermis and hair follicles in the skin in both mouse strains. Expression of apoA-II mRNA in those tissues was also examined by RT-PCR analysis. Immunolocalization of apoA-II protein also indicated the cellular localization of apoA-II. ApoA-II transcription was not observed in the heart. Amyloid deposition was observed around the cells expressing apoA-II mRNA in the old R1.P1-Apoa2 c mice. These results demonstrate that the apoA-II mRNA is transcribed and translated in various extrahepatic tissues and suggest a possible contribution of apoA-II synthesized in these tissues to amyloid deposition.

Stromal sarcoma of the breast with leiomyosarcomatous pattern.

We report an unusual case of stromal sarcoma of the breast with leiomyosarcomatous pattern, which recurred locally and was finally treated by radical mastectomy. The tumor was composed of pleomorphic and hyperchromatic spindle‐shaped cells arranged in an interdigitating fascicle. The nuclei were of moderate to severe atypia. An average of 10 mitoses per 10 high‐power fields was seen. Immunohistochemically, the stromal cells were positive for vimentin and α‐smooth muscle actin, but negative for S‐100 protein, cytokeratin and desmin. The average Ki‐67 (MIB1) labeling index in the stromal cells was 34%. Electron microscopic evaluation revealed further evidence of smooth muscle differentiation; stromal cells had frequently indented nuclei, well‐developed rough endoplasmic reticulum, thin basal lamina and dense patch‐like structures within the cytoplasm. Analysis of previous literature on 17 cases reveals mitotic activity of the tumor seemingly of little prognostic value. This case indicated difficulty in diagnosing leiomyosarcoma. The risk of local recurrence remains even if the surgical margin is free of tumor cells.

A case of Occult Breast Cancer with Paraneoplastic Polyneuropathy

We encountered a very rare case of occult breast cancer associated with paraneoplastic sensory polyneuropathy.A 59-year-old woman was admitted to our hospital complaining of numbness in all extremities, ataxia of left extremities and a tumor in the left axilla. From the neurological findings, a malignant tumor was suspected. The immunohistochemical analysis of the axillar swollen lymph node revealed metastasis from breast cancer and confirmed the primary lesion. On a preoperative diagnosis of suspected occult breast cancer, left mastectomy and resection of left axillar lymph nodes were performed. Furthermore, immunohistochemical staining of sural nerves and Western blot analysis of the serum of this patient showed the loss of axons and the presence of antineural antibody in the serum.Immunological response was considered to be the remote effector system between the breast cancer and sensory polyneuropathy in this disorder.

Can cytological findings predict intraductal spread of breast cancer? Histopathological case–control study

An important predictive factor for local recurrence after breast‐conserving therapy is the state of the surgical margin. In order to obtain a negative surgical margin, the present case–control study was conducted to determine whether the extent of ductal spread can be estimated from the information obtained by fine‐needle aspiration (FNA). Samples from 69 cases of extensive ductal spread (EDS) in which it was thought that cancer cells had remained in the residual breast when the lumpectomy was performed with 2 cm margins, were retrieved and compared with 62 cases having almost the same clinical and pathological tumor size. The cases of EDS included a significantly larger number of papillotubular carcinomas (37%vs 13%, P = 0.004) and displayed a high nuclear atypia (42%vs 26%, P = 0.001). We could estimate the same tendency with cytological studies. Cancer cells with cohesive papillary‐like clusters suggesting papillotubular carcinoma and with a large nuclear diameter were significantly more numerous in cases of EDS (P < 0.01). In conclusion, EDS can be determined by estimating histological type via cytodiagnosis and measuring the nuclear diameter of cancer cells.

Bilateral synchronous spindle cell, apocrine and scirrhous carcinoma breast cancer in a case or malignant lymphoma

An unusual case of synchronous bilateral breast cancer occurring during combination chemotherapy and radiation to the outside of the breast for malignant lymphoma is reported. Two histologically rare carcinomas, spindle cell carcinoma and apocrine carcinoma, were observed in this case. A 77-year-old woman, who had been treated for stage IIIA non-Hodgkin’s lymphoma, developed bilateral breast tumors. Aspiration biopsy cytology findings of the tumor in the left breast showed several clusters of adenocarcinoma cells and some large atypical spindle shaped cells, which suggested spindle cell carcinoma. The cytologic findings of the right breast tumor were highly suggestive of scirrhous carcinoma. A modified radical mastectomy was performed on both breasts. Pathological examination disclosed two separate cancer lesions in the left breast. The lesion which had been detected before the operation, was a spindle cell carcinoma. Another lesion, detected for the first time by pathological examination, was an apocrine carcinoma. The lesion in the right breast was a scirrhous carcinoma. Since non-invasive foci were detected in these three cancer lesions, each lesion was thought to be a primary cancer. All dissected bilateral axillary lymph nodes showed malignant lymphoma. Immuno-histochemistry of the spindle cell carcinoma revealed positive immunoreactivity for cytokeratin, which suggested the epithelial as well as mesenchymal nature of this tumor. Synchronous existence of malignant lymphoma and three independent breast cancers including spindle cell carcinoma and apocrine carcinoma is very rare.

Consideration of breast diseases diagnosed as class III by aspiration biopsy cytology : Comparison of class III a with class III b groups

過去7年3ヵ月間に長野県がん検診センターの乳腺外来で穿刺吸引細胞診 (ABC) を施行した乳腺疾患1,215例中の乳癌症例295例に対するABCの正診率は86.1%であり, 良性疾患917例の正診率は83.3%であったが, class III判定がおのおの14例, 4.7%および62例, 6.8%にみられた. class III症例76例をclass III a 51例とclass III b25例に分けて比較検討した結果 以下の結論を得た.1) class III症例中のclass III bの割合は乳癌が64.3%と最も多く, ついで乳腺症が40.9%で, 線維腺腫は9.5%と少なかった.2) class III a群中の乳癌比率は9.8%であり, class III b群では36.0%であった.3) 触診で乳癌と診断した群では差がみられなかったが, 乳腺症と診断した群ではclass III b群の方がclass III a群より乳癌比率が高かった.4) Mammography診断が良性 (I・II) で, ABCがclass III aの場合には乳癌はなかったが, class III bの場合には1/3強が乳癌であった. 悪性 (IV・V) の場合はclass III aでも乳癌の可能性が高かった.5) Echography診断が良性～疑診 (I～III) で, ABCがclass IIIaの場合には乳癌は少なかったが, class III bの場合には30%弱が乳癌であった. 悪性 (IV・V) の場合はclass III a, III bに関係なく乳癌であった.6) Thermography診断が良性 (I・II) で, ABCがclass III aの場合には乳癌は少なかったが, class III bの場合は1/3が乳癌であった. 悪性 (IV・V) の場合はABCがclass III bの場合は半数が乳癌であった.以上の成績からABCのclass III判定例をclass III aとclass III bに分ける意義が窺われた.