Hiroyuki Kusano

Gain of chromosome 20 is a frequent aberration in liver metastasis of colorectal cancers

To investigate the characteristics of thenumerical chromosome aberrations in liver metastasis ofcolorectal cancers, fluorescence in situ hybridization(FISH) for chromosomes 8, 18, 14/22, and 20 wasperformed in 18 specimens of primary regions and 18 ofmetastatic regions in liver metastasis of colorectalcancers compared with 15 of non-liver metastaticcancers. Among these numerical aberrations, the gain of chromosome 20, especially copy numbersexceeding three, was frequently observed in primary andmetastatic cancers. Among these numerical aberrations,the gain of chromosome 20, especially copy numbersexceeding three, was frequently observed in primary andmetastatic regions of liver metastasis groups comparedwith that of the non-liver metastasis group (P <0.05). The incidences of gain of chromosome 20 in both regions of the liver metastasis group werehigher than that of the non-liver metastasis group (P< 0.05). The gain of chromosome 20 is a frequentaberration in primary and metastatic regions in patients with liver metastatic colorectal cancers andmay be available as a genetic marker for the diagnosisor prediction of liver metastasis.

Anal metastasis from carcinoma of the lung: report of a case.

We report herein the case of a 75-year-old man who developed anal canal metastasis from squamous cell carcinoma of the lung. Initially, he underwent a right middle and lower lobectomy combined with left atrial wall resection under cardiopulmonary bypass. He presented 3 months later with an anal polyp which had prolapsed and bled, for which he underwent a transanal polypectomy. Histologically, the polyp was classified as squamous cell carcinoma and considered to be a metastasis from the primary lung cancer. He is presently well with no signs of recurrence 9 months after his initial operation. To our knowledge, there has been no other case of anal metastasis from lung cancer ever reported.

An immunohistochemical employer monoclonal antibodies against Lea, sialyl Lea, Lex, and sialyl Lex antigens in primary colorectal, carcinomas and lymph node and hepatic lesions

The immunohistochemical expression of sialylated and non-sialylated forms of both Lex and Lea were studied in 87 carcinomas and 42 normal mucosal specimens of colon and rectum, as well as in 32 metastatic lymph nodes and 9 hepatic lesions, using an indirect immunoperoxidase staining. Their antigens were expressed in normal mucosa with the following frequencies: Lea, 95.2% (40/42); sialyl Lea, 88.1% (37/42); Lex, 95.2% (40/42); and sialyl Lex, 17.0% (7/42), whereas in carcinomas, the respective rate of frequency were: 78.2% (68/87); 78.2% (68/87); 90.8% (79/87); and 93.1% (81/87). Sialyl Lex antigen showed the highest tumor specificity compared to other antigens. In three normal mucosal specimens and four carcinomas with Le(a−b−) phenotype, the expression of type 1 antigens (Lea and sialyl Lea) was not consistent, whereas type 2 antigens (Lex and sialyl Lex) were consistently observed in carcinomas. The staining of type 1 antigens and Lex was decreased in metastatic lesions compared with primary carcinomas, whereas sialyl Lex antigen had the same positive-staining rate in both. Metastatic carcinoma expressed the sialylated form more predominantly than the non-sialylated form in type 2 antigens whereas the opposite result was observed in type 1 antigens. These results suggested that: (a) sialyl Lex, defined by monoclonal antibody CSLEX1, may be useful as a tumor-associated antigen in colorectal carcinoma, and (b) the alteration of Lewis-related carbohydrate antigens in cancer cell membranes, including sialylation and/or aberrant glycosylation, may be related to metastatic behavior.

Quantitative analysis of numerical chromosome aberrations in various morphological types of colorectal carcinomas

Quantitative analysis by fluorescence in situ hybridization (FISH) on thin paraffin-embedded tissue sections, using specific probes for chromosomes 11, 17, and 18 was employed in various morphological types of early and advanced colorectal cancer to clarify tumor cytogenetics. The chromosome index (CI) was calculated as a quantitative measure of the chromosome copy number. Compared with the CI of normal epithelium, the CI of chromosome 11 in villous components of adenomas or polypoid early cancers was decreased, while the CI in flat type or advanced colorectal cancers, conversely, was increased (P<0.05). The CI of chromosome 17 in villous components of adenomas and all cancers was higher than that of normal epithelium (P<0.05), but the differences were not significant. In protruding advanced cancers, the CI of chromosome 18 was significantly decreased (P<0.01) compared to the CI of normal epithelium. There was no significant chromosomal heterogeneity between the superficial and the deepest layer in each cancer. In mucosa adjacent to sessile and flat type cancers, the CI of chromosome 17 was significantly higher than the CI in normal epithelium or adenomas (P<0.05). These results suggest that numerical chromosome aberrations are associated with the histological type of adenoma and the morphological diversity of cancer in the colorectum, and that chromosome 17 abnormality occurs in mucosa adjacent to sessile and flat cancers.

Serological and immunohistochemical studies on sialylated carbohydrate antigens in colorectal carcinoma

SummarySialylated carbohydrate antigens, such as CA19-9 (sialyl Lea), CA-50 (sialyl Lc4), CSLEX1 (sialyl Lex) and SLX (sialyl Lex-i), were assayed in the same preoperative serum samples of 63 patients with colorectal cancer, and compared with CEA. In addtion immunohistochemical expressions of sialyl Lea, sialyl lex and sialyl Lex-i antigens were studied in 62 colorectal carcinomas and 42 normal mucosal sites remote from the malignant lesion using monoclonal antibodies CSLEA1, CSLEX1 and FH-6, respectively, in order to elucidate their tumor-specificity and clinical usefulness as a tumor-associated antigen. Serologically, the percent positive rates of CA19-9, CA-50, CSLEX1, SLX and CEA were 30.2%, 17.7%,23.8%, 16.1% and 44.4%, respectively. In dukes’ A and B, these sialylated carbohydrate antigens, especially CSLEX1 and SLX, showed low positive rates, but the percent positive rates of CSLEX1 and SLX correlated with operative radicality. The positive spectrum of CSLEX1 differed from that of CA19-9 in sera, and CEA had no correlation with these two antigens. The immunohistochemical expression rates of sialyl Lea, sialyl Lex and sialyl Lex-i were 88.1%, 17.0% and 9.5% in normal mucosa, but were 77.8%, 90.5% and 71.4% in carcinoma, respectively. These data suggested that the type 2 chain antigens CSLEX1 and SLX, which have high tumor-specificity compared with CA19-9, may be useful in preoperative diagnosis for extention of carcinoma and operative radicality, althogh early diagnosis using these sialylated carbohydrate antigens may be difficult, while the combined use of CA19-9, CSLEX1 and CEA should make it possible to detect a wide range of colorectal cancer patients.

Cholecystitis caused by a fish bone

The accidental ingestion of a foreign body is not uncommon. However, the presence of a foreign body in the gallbladder is extremely rare. Here, we present a case of cholecystitis due to a fish bone that may have penetrated through the stomach wall and into the gallbladder without causing peritonitis. A laparoscopic cholecystectomy was performed; a fish bone, measuring 4.0 cm in length, was found in the gallbladder. To the best of our knowledge, this is the first such case to be reported.

An immunohistochemical study of the distribution of blood group substances and related antigens in primary colorectal carcinomas and metastatic lymph node and liver lesions, using monoclonal antibodies against A, B, H type 2, Lea, and Lex antigens

Using indirect immunoperoxidase staining, we examined the distribution of blood group substances and related antigens, including Lea, A, B, H type 2, and Lex, in 87 carcinomas and 42 normal mucosal specimens of colon and rectum, as well as in metastatic lesions of 32 lymph nodes and 9 liver specimens. The compatible expression rate of A/B/H type 2 antigens was 33.3% (3/9) in proximal normal colon, but only 6.1% (2/33) in distal normal colon. Compatible expression was observed in 14 of 25 carcinomas in the proximal colon (56.0%), but these antigens in distal colon cancers reappeared with a high positive rate, 62.9% (39/62). The rate of H type 2 accumulation with the deletion of A and/or B antigens was 6.9% (6/87). Incompatible expression was not observed in colorectal cancer. Lea and Lex antigens were expressed in normal mucosa and primary carcinoma throughout the colon. Lea and Lex in primary carcinoma that showed A/B deletion with/without H type 2 accumulation was expressed more than in carcinoma with A/B/H type 2 compatible expression (88.2% vs 71.7% for Lea; 94.1% vs 88.7% for Lex, respectively). In 16 of 32 patients (50.0%), A/B/H type 2 antigen expression in metastatic lesions had disappeared or was decreased compared with that in primary carcinoma, followed by metastasis to regional lymph nodes. These results suggested that: (a) A/B/H type 2 blood group substances in the distal colon behave as tumor-associated antigens in colorectal carcinoma. (b) Most frequently, A/B/H type 2 antigens expressed in primary carcinoma were weakened or had disappeared in metastatic lymph nodes. Further investigation of the biological function of carbohydrate chains, such as those of blood group substances and related antigens on cancer cell surfaces may lead to a solution of the problem of the metastatic behavior of tumor cells.

Different expressions of sialyl Tn antigen between polypoid and flat-type early colorectal cancers

PURPOSE: Sialyl Tn (STn) antigen is a cancer-associated carbohydrate antigen expressed in cancers of the digestive tract. We compared the proportion of specimens of flat-type colorectal cancers expressing STn with that of polypoid cancers, by examining the immunohistochemical reactivity of STn in various morphologic types of early and advanced colorectal cancers. METHODS; A total of 111 biopsies from the colorectal area were examined for STn expression, including 11 adenomas, 58 early cancers, and 42 advanced cancers. Each section was stained immunohistochemically for STn antigen. In each section, we examined STn expression in the cancer area, adjacent mucosa, and normal epithelium. RESULTS: STn expression was detected in 90.9 percent of adenomas, 36.2 percent of early cancers (T1), 64.3 percent of advanced cancers (>T1), and 52 percent of mucosa adjacent to cancer. The morphology of cancer tissue did not influence the number of specimens exhibiting STn antigen expression in mucosa adjacent to cancer cells. STn antigen was rarely expressed in flat or depressed-type early cancers (T1; 7.1 percent), and the expression was higher in moderately than in well-differentiated adenocarcinomas. In advanced cancers (>T1), a similar proportion of protruding and small ulcerative cancers expressed STn. CONCLUSION: Our results suggest that the low expression of STn antigen in flat-type cancers may be the result of different mechanisms of cellular transformation during carcinogenesis from the usual adenoma-carcinoma sequence in colorectal neoplasms.

Signet ring cell early gastric cancer presenting as an elevated lesion.

SummaryEarly gastric cancer composed of signet ring cell carcinoma is usually present as a depressed lesion and rarely manifests as a protruding lesion. To our knowledge, only eight cases have been reported in the literature. We herein report such a rare lesion which developed in an asymptomatic 55-year-old man.

ISOLATED ADRENOCORTICOTROPIC HORMONE (ACTH) DEFICIENCY

The case to be reported is that of a 72‐year‐old woman with isolated adrenocorticotropic hormone (ACTH) deficiency, who complained of anorexia and generalized malaise. The secretions of human growth hormone(HGH), prolactin (PRL), luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) were all within normal limit. In spite of the extremely low level of Cortisol, the plasma level of AGTH would not rise sufficiently, but a marked response of Cortisol to AGTH stimulation was recognizaed. The postmortem examination revealed a decrease In basophilic or PAS‐positive cells of the anterior pituitary gland which also showed a selective loss of AGTH‐secreting cells over immunohistochemical study. Electron microscope could easily visualize somatotroph, mammotroph, thyrotroph, FSH‐ and LH‐gonadtroph, but corticotroph was difficult to be discerned. Adrenocortical cells demonstrated atrophy and degeneration, for which the zona fasciculata and zona reticularis were narrowed. The zona glomerulosa was slightly enlarged In width.