Atsuo Tsuchiya

Immunohistochemical detection of lymph node microinvolvement in node-negative gastric cancer

Abstract:Background. Despite curative resection of the primary tumor with extensive dissection of lymph nodes, some patients with node-negative gastric cancer die of local relapse or metastatic disease. Microinvolvement of regional lymph nodes may play an important role in the prognosis.Methods. To evaluate the incidence and prognostic implications of regional lymph node microinvolvement in node-negative gastric cancer, we retrospectively analyzed tissue samples from 51 patients operated on for primary gastric cancer. They had tumors that invaded beyond the muscularis propria, but without metastasis to the lymph nodes, shown by the conventional H&E staining method. The regional lymph nodes were examined immunohistochemically, using monoclonal antibodies against cytokeratin.Results. Microinvolvement was found in 4.8% of lymph nodes (67/1390) and in 43.2% of the patients (22/51). The clinical outcome of the patients with microinvolvement was not significantly different from those without it. However, no patient died in the no-microinvolvement group, while three patients in the microinvolvement group died of recurrence.Conclusion. The incidence of microinvolvement in conventionally negative lymph nodes cannot be ignored, and detecting microinvolvement may be important for predicting recurrence of gastric cancer.

High proportion of missense mutations of the BRCA1 and BRCA2 genes in Japanese breast cancer families

AbstractMutations in either of two recently identified genes, BRCA1 and BRCA2, are thought to be responsible for approximately two-thirds of all cases of autosomal-dominantly inherited breast cancer. To examine the nature and frequency of BRCA1 and BRCA2 mutations in Japanese families exhibiting a high incidence of breast cancer, we screened 78 unrelated families in this category for mutations of these two genes. Examining the entire coding sequences as well as exon–intron boundaries of both genes by polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) and multiplex-SSCP analysis, we identified possible disease-causing alterations in BRCA1 among affected members of 15 families and in BRCA2 in another 14 families. In 15 of those 29 families, the affected individuals carried missense mutations, although most germline mutations reported worldwide have been deletions or nonsense mutations. Our results, indicating that missense mutations of BRCA1 and BRCA2 tend to predominate over frameshifts or nonsense mutations in Japanese breast cancer families, will contribute signifi-cantly to an understanding of mammary tumorigenesis in Japan, and will be of vital importance for future genetic testing.

INHIBITORY EFFECTS OF PROSTAGLANDIN D2 AGAINST THE PROLIFERATION OF HUMAN COLON CANCER CELL LINES AND HEPATIC METASTASIS FROM COLORECTAL CANCER

The inhibitory action of prostaglandin D2 (PGD2) and its effect on the cell cycle were examined in cell lines SW480 and LS174T of human colon cancer. The growth of the cell lines were assessed 24h and 48h after the addition of 1.0μg/ml and 10.0μg/ml PGD2. The growth of SW480 cells and 24h and 48h after the addition of 10.0μ/ml, while that of LS174T was inhibited by both doses after 24h and 48h. S-Phase DNA synthesis in the SW480 cells was significantly blocked 24h after the addition of 10.0μg/ml PGD2. The cell cycle of LS174T cells was arrested at the G0+G1 phase 24h after the addition of 1.0μg/ml and 10.0μg/ml PGD2. The correlation between hepatic metastasis and PGD2 concentration in human cancer tissue was examined. The mean value of PGD2 concentrations in the primary cancer tissue was significantly lower in the hepatic metastasis group than that in the group without hepatic metastasis. These findings suggest that measuring the PGD2 in cancer tissue may be useful for detecting and predicting the hepatic metastasis from human colorectal cancer.

Breast Cancer in Two Patients with Poland's Syndrome.

Poland’s syndrome is characterized by a congenital defect of the pectoralis major associated with various types of anomalies of the ipsilateral upper extremity. Furthermore, there have been reports of Poland’s syndrome associated with malignancies such as leukemia, malignant lymphoma, and leiomyosarcoma. We describe two cases of Polands syndrome associated with breast cancer. The first patient developed right breast cancer associated with ipsilateral breast hypoplasia, defects of the pectoralis major and minor, and syndactyly. She underwent mastectomy and dissection of the axillary nodes. The second patient had left breast cancer associated with ipsilateral breast hypoplasia, defects of the pectoralis major and minor, and syndactyly. She underwent breast-conserving surgery and dissection of the axillary nodes without irradiation of the breast. Both patients are currently alive and free of disease. Although previously there has been no evidence that links Poland’s syndrome and breast cancer, elucidating the molecular mechanism that causes Polands syndrome may further clarify the relationship between Poland’s syndrome and malignancies.

Malignant rhabdoid tumor of the colon: report of a case.

A malignant rhabdoid tumor of the colon is very rare and only three cases have been previously described. A 76-year-old man was admitted to the hospital complaining of epigastralgia. An elastic mass was palpable in the right upper abdomen. A barium enema and endoscopic examination showed a giant gyrate tumor arising from the cecum. Abdominal ultrasonography and a computed tomography scan revealed the tumor to be located in the colon associated with multiple liver metastases and gallbladder stones. A right colectomy and cholecystectomy were thus performed. The tumor was histologically composed of sheets of large round and polygonal nuclei with vesicular chromatin, and abundant acidophilic cytoplasm, often containing hyalin-like inclusion. The cytoplasm was positive for vimentin and neuron-specific enolase, and hyaline globules of the rhabdoid tumor cells stained positive for cytokeratin in some cells. Transmission electron microscopy showed characteristic rhabdoid cells with an aggregation of intermediate filaments. A histologic diagnosis of malignant rhabdoid tumor of the colon was made. The tumor demonstrated several unusual findings for malignant rhabdoid tumors including diploidy by a flow cytometric analysis, and positive nuclear immunohistochemical staining for p53 protein and Ki-67 antigen. We report herein the third known case of a pure colonic rhabdoid tumor.

Venous Invasion as a Prognostic Factor in Colorectal Cancer

Venous invasion as a prognostic factor was evaluated in 124 patients with colorectal cancer. By classifying the patients as having either negative to mild invasion or moderate to marked invasion, a significant correlation was found between the degree of venous invasion and clinicopathological variables such as lymphatic invasion, lymph node metastasis, liver metastasis, and DNA ploidy. Significantly more favorable survival was seen in those with a lower degree of vascular invasion; however, of the six prognosticators analyzed by Coxs proportional hazard model, the only significant factors were depth of invasion and DNA ploidy. Although venous invasion showed no significance, it is still considered a valuable prognostic indicator that is easy and economical to perform.

Prognostic factors associated with differentiated thyroid cancer

A multivariate analysis was conducted on the survival data of 180 patients who underwent curative resection for differentiated thyroid cancer between 1966 and 1987, and the 10- and 20-year survival rates were found to be 80.6% and 73.1%, respectively. A survival analysis was also performed, testing the following factors: the patients age at the time of diagnosis, tumor size, extraglandular extension, nodal status, distant metastases, operative procedure, sex, and histology. A univariate analysis found the initial six factors to be significant prognostic variables, but the latter two to be of no significance. On the other hand, the multivariate analysis showed that distant metastases, age, and tumor size were the most significant prognosticators. Thus, the age of the patient should be taken into consideration during the follow-up of treatment for differentiated thyroid cancer.

Adenoendocrine cell carcinoma of the gallbladder: report of a case.

Adenoendocrine cell carcinoma of the gallbladder is an uncommon form of cancer. We treated a 36-year-old woman who came to us with a chief complaint of abdominal pain. The abnormality was diagnosed to be a tumor-like mass in the gallbladder, and adenomyomatosis of the gallbladder was strongly suspected. A laparoscopic cholecystectomy was successfully performed, and the histopathological finding was adenoendocrine cell carcinoma of the gallbladder. The tumor cells of the small round cell carcinoma partly stained positively for synaptophysin, neuron-specific enolase, and CD 56, while adenocarcinoma cells showed positive reactions to keratin, which was thus suggestive of adenoendocrine cell carcinoma. The patient is alive and doing well at 12 months after the treatment.

The neurosurgical management of brain metastasis from colorectal cancer: A report of three cases

We report herein three cases of brain metastasis from primary colorectal cancer in which the metastatic lesion was resected to effectively relieve neurological symptoms. Case 1 was a 61-year-old woman with a solitary brain metastasis from colorectal cancer and no other metastases; case 2 was a 59-year-old woman who died from liver metastasis 11 months after resection of the metastatic brain tumor; and case 3 was a 68-year-old woman with multiple metastases to the lungs and bones detected before the brain metastasis. According to 16 cases previously reported in the Japanese literature and our 3 cases, the interval between diagnosis of the primary cancer and discovery of brain metastasis was 23 months on average, while the median survival after the discovery of brain metastasis was 7 months. Brain metastases with liver and lung metastases were seen more frequently than brain metastases alone. In these three cases, chemotherapy appears to have been of no use in preventing recurrence. Thus, we believe neurosurgical management to be appropriate for a solitary lesion and that it should be actively pursued to prolong survival and improve quality of life.

Immunohistochemical Evaluation of Lymph Node Micrometastases from Breast Cancer

The lymph node micrometastasis was retrospectively immunohistochemically investigated in 185 patients with node-negative breast cancer and compared with the routine conventional findings. The monoclonal antibodies to epithelial membrane antigen (EMA) and mucinous-like carcinoma antigen (MCA) were used. Of 19 EMA-positive cases, 16 were false positive. Therefore only 3 cases were found to show staining with both EMA and MCA. The patients are all living and well and free of recurrence. No micrometastasis was immunhistochemically demonstrated in 11 node-negative breast cancer patients with subsequent metastases. The results of the present study indicate that the detection rate containing occult cells afforded by conventional routine evaluation is sufficient, at least in Japanese.