Radioimmunoassay of carcinoembryonic antigen in extracts of human colon and stomach

Radioimmunoassay is used to characterize and quantitatively determine CEA in perchloric extracts of human stomach and intestine, normal, foetal or cancerous. High concentrations of CEA were found in primary adenocarcinomas of the colon and in their metastases to liver. CEA could also be detected, in lesser amounts, in six colonic mucosa removed for non-cancerous diseases, in two specimens of foetal gut and in five out of six gastric carcinomas. On the other hand, CEA could not be found in non-cancerous gastric mucosa. Comparison of inhibition curves shows that CEA present in non-cancerous colon and purified CEA isolated from metastatic colonic cancer have the same immunological reactivity.     

c-K-ras mutations in human carcinomas occur preferentially in codon 12

A study was carried out to determine the frequency and distribution of mutations in the c-K-ras gene in human carcinoma tissue. The study was done on a total of 51 lung, colon and breast carcinoma tumors using a panel of oligonucleotides coding for the wild type and all possible mutations in codons 12 and 61 of c-K-ras gene. Four of 16 colon carcinomas, two of 27 lung carcinomas and one of eight breast carcinomas were found to contain mutations in codon 12. No mutations were found at position 61. Of the six possible amino acid replacements in codon 12, all but one was represented in the seven mutations identified.     

Carcinoma-related alterations of glycosyltransferases in human tissues

The glycosyltransferases responsible for catalyzing additions of A, B, and H sugars to cellular acceptors were studied in 23 cases of primary carcinoma. The carcinomas were derived from mouth, tongue, larynx, lung, cervix, esophagus, stomach, and colon. Comparisons of A, B, and H enzymes were made between mucosal extracts from tumor and from normal adjacent tissue and, in the case of gastrointestinal tract, extracts derived from mucosae of individuals free of disease. The most prevalent finding was that of alpha-2-fucosyltransferase (H enzyme) deficiency in tumor extracts from Group A, B, and O patients in relation to the normal tissue counterpart (20 cases). Exceptions were observed in one case of carcinoma of the stomach and in two of seven cases of carcinoma of rectum or sigmoid. In four of nine Group A patients (carcinoma of the mouth, tongue, ascending and transverse colon), N-acetylgalactosaminyltransferases (A enzymes) were demonstrated but were deficient in relation to the normal adjacent counterpart. A enzymes were not demonstrable in normal and tumor extracts from distal colon in five cases. Differences between tumor extracts and normal adjacent tissue were noted in D-galactosyltransferase (B enzyme) derived from carcinomas of larynx and esophagus, but B enzyme was not demonstrated in tumor or normal tissue derived from the sigmoid colon. Study of the normal distribution of H enzyme in gastrointestinal mucosa indicated the presence of relatively high enzyme levels in stomach and upper intestine but low levels in distal colon.     

Initial phase of Borrmann type-IV carcinoma of the stomach suggested from observations of early gastric carcinoma arising in breast cancer patients

Borrmann Type-IV carcinomas were frequently found in advanced carcinoma of the stomach arising in breast cancer patients as a second malignancy. We assumed that some of the early gastric carcinomas in with breast cancer patients would develop into Borrmann Type-IV carcinoma. According to histopathological studies involving 10 cases, six were presumed to be initial lesions of Borrmann Type-IV carcinoma. All lesions in the six cases were macroscopically Type-IIc of early gastric cancer. A shallow ulcer scar, such as UL-1 or UL-II was mostly observed in IIc lesions.     

A monoclonal antibody reacting with various human carcinomas and fetal colon and esophagus

A monoclonal antibody 9A3 was raised to human gastric carcinoma cell line TMK-1, a poorly differentiated adenocarcinoma of the stomach. 9A3 antibody (IgG1, kappa) strongly reacted with various carcinomas immunohistochemically, but did not react with any normal tissues of the whole body tested except for neutrophiles and macrophages. 9A3 antibody also reacted with the luminal surface of the fetal colon and esophagus at six months of gestation. The antigen recognized by 9A3 antibody might be an oncodevelopmental antigen.     

Increase of phosphotyrosine-containing proteins in human carcinomas

Immunofluorescent (IF) staining with monoclonal antibody to O-phosphotyrosine (PTYR) has shown that a variety of human carcinomas (liver, esophagus, stomach, lung, colon and breast) have increased amounts of PTYR-containing proteins (PTYR-proteins), which are localized in cytoplasmic regions and nucleolus-like structures of the carcinoma cells. PTYR-proteins were isolated from carcinomas of the liver, stomach and esophagus, and also from normal regions of these organs by immunoaffinity chromatography with polyclonal antibodies to PTYR. They were then labeled with 125I and analyzed by gel electrophoresis. Twenty-eight species of PTYR-proteins in a molecular weight range from 310,000 to 23,000 were detected, of which the major 16 species were confirmed to contain 125I-labeled diiodo-O-phosphotyrosine residues. All the PTYR-proteins found in carcinomas were also present, though at much lower levels, in normal regions of the respective organs.     

Gastrin Receptor Gene Expression in Several Human Carcinomas

Gastrin has been shown to enhance the growth of various human tumors. The present study was designed to examine the gastrin receptor gene expression in various human carcinoma cell lines and in surgically resected carcinoma tissues. By Northern blot analysis, gastrin receptor mRNA was detected in 3 out of 7 small cell lung carcinoma cell lines. Gastrin receptor mRNA was also expressed in one out of 8 colon carcinoma cell lines and 2 out of 10 colon carcinoma tissues. Moreover, one of two small cell carcinoma cell lines of the stomach clearly expressed gastrin receptor mRNA. However, none of the gastric adenocarcinoma cell lines or surgically resected gastric adenocarcinomas tested had any detectable expression of gastrin receptor gene. These findings may suggest a role of gastrin receptor in the growth and differentiation of certain human carcinomas.     

Tumor-specific methylation patterns of erbB2 (HER2/neu) sequences in gastro-intestinal cancer.

To determine whether the sporadically occurring amplification of the oncogene erbB2/HER2 in gastrointestinal carcinomas is associated with additional changes of this sequence, DNA from 17 colorectal and 5 stomach carcinomas was analyzed for copy number, sequence rearrangement and DNA methylation by Southern blot hybridization. Amplification was detected in two cases. By applying the isochizomers Hpall and Mspl we tested for alterations in the DNA methylation status. Whereas in colon tumors with non-amplified erbB2 this status was unchanged, one case with erbB2 amplification showed additional MspI bands indicating a methylation of the amplified gene sequences. In stomach carcinoma, however, we detected differences between tumor and mucosa samples but not between amplified and non-amplified tumor samples. Independent of the DNA methylation status, significant amounts of the erbB2 oncoprotein were detected in the cases with gene amplification; weaker immunostaining of erbB2 was also seen in a few additional tumors.     

A radioimmunoassay for the detection of a human tumor-associated glycoprotein (TAG-72) using monoclonal antibody B72.3

Monoclonal antibody (MAb) B72.3 was generated against a carcinoma metastasis and has been shown to bind with a high degree of selectivity to a tumor-associated glycoprotein (TAG-72) found in human colon and breast carcinomas, while showing minimal reactivity to any normal adult tissues. Competition radioimmunoassays have been developed for the detection of TAG-72 in tumors and sera from both athymic mice bearing human carcinoma xenografts and patients with colon, breast and other carcinomas. The distribution of TAG-72 in human tumor xenografts was restricted to tumors originating from the LS-174T human colon carcinoma, with no significant reactivity being detected in human tumor xenografts from a different colon carcinoma, a human breast carcinoma, or a human melanoma. The levels of TAG-72 in clinical material obtained from surgery were examined; high levels were found in colon carcinomas and to a lesser extent in breast carcinomas, while no detectable levels were found in normal tissues. Sera from apparently normal patients contained a mean level of 2.2 units per ml of TAG-72. A level of 3 standard deviations above the mean level of TAG-72 found in normals was employed as a cut-off value to indicate a positive test result in subsequent studies. No patient with inflammatory disease or other benign colon disease exhibited elevated levels of TAG-72. Seven out of 20 patients with other carcinomas had elevated serum levels of TAG-72. The serum TAG-72 levels were compared with the serum levels of antigens recognized by the MAbs currently used to screen sera of carcinoma patients (CEA, GICA, and OC125). It was clearly demonstrated that TAG-72 is different from these antigens and can be found in some sera in which no antigen is detected by otherwise available MAb RIAs.     

Comparison of matrix metalloproteinase expression between primary tumors with or without liver metastasis in pancreatic and colorectal carcinomas

BACKGROUND AND OBJECTIVES: Matrix metalloproteinases (MMPs) are known to play an important role in carcinoma cell invasion and hematogenous metastasis by mediating the degradation of the extracellular matrix. METHODS: We investigated the relationship between MMP-2 and -9 enzymatic activities and liver metastases in human pancreatic and colon carcinomas, using xenograft tumors in nude mice. RESULTS: We found that type IV collagenase activity in pancreatic and colon carcinomas with liver metastases was significantly higher than in pancreatic and colon carcinomas without liver metastases. Gelatin zymography showed the presence of gelatinolytic activity bands at M(r) 92,000 and 72,000, indicating MMP-9 and MMP-2, respectively. MMP-2 and -9 expression levels in pancreatic and colon carcinomas with liver metastases were higher than in pancreatic and colon carcinomas without liver metastases. TIMP-2 levels in pancreatic and colon carcinomas with liver metastases were also higher than in those without liver metastases. CONCLUSIONS: MMP-2 and MMP-9 expression in primary tumors is associated with liver metastases in pancreatic and colon carcinomas. In addition, the balance of activity between MMP-2, MMP-9, and TIMP-2 may be relevant to carcinoma invasion and metastasis, including liver metastases in pancreatic and colon carcinoma.     

The Value of CA 19-9 in Gastric and Colorectal Carcinoma

We have conducted a prospective study of 441 patients, to investigate the utility of a new tumor marker CA 19-9 for the diagnosis and monitoring of patients with cancer of the gastrointestinal tract (93 patients with colorectal carcinoma, 57 with carcinoma of the stomach, 10 with esophageal carcinoma, 45 with malignancies outside the gastrointestinal tract, and 236 with benign general surgical disease). Results were compared to those obtained for carcinoembryonic antigen (CEA) in the diagnosis of carcinoma of the stomach and colon/rectum. CEA is more sensitive than CA 19-9 in all stages of carcinoma of the stomach and colon/rectum. During treatments of gastrointestinal carcinomas, CEA and CA 19-9 were determined at the same time in 66 and 165 patients with surgically treated carcinoma of the stomach and colorectal carcinoma, respectively. It was noted that CEA is more sensitive than CA 19-9 in detecting recurrence. However, CA 19-9 is more specific. The best results were obtained when both markers were used together.     

Relationship between cholecystectomy and the subsequent development of colorectal carcinoma

In order to clarify the presence or absence of a relationship between cholecystectomy and the subsequent development of colorectal carcinoma, we compared the incidence of previous cholecystectomy in 448 patients with colorectal cancer and in 1627 with gastric cancer, who had been treated in our clinic during the 21 year period through 1963 to 1983. There was no statistically significant difference in the incidence of previous cholecystectomy between patients with colorectal and gastric cancer. We then performed an historical cohort study covering 461 patients undergoing cholecystectomy for gallstone during the 32 year period from 1949 to 1981 for the subsequent occurrence of carcinoma of the colorectum and stomach. The observed incidence was one in colon cancer and six in gastric cancer, showing a similar proportion of the development of both carcinomas in our district. The present study showed no evidence of cholecystectomy being an increased risk for the development of colorectal carcinoma.     

Krukenberg tumors of the ovary: a clinicopathologic analysis of 27 cases

A series of 27 typical Krukenberg tumors of the ovary were analyzed. By definition, all examples were characterized by the presence of mucinous signet-ring carcinoma cells within a cellular, nonneoplastic ovarian stroma. The patients' ages ranged from 20-70 years; almost one-half were 40 years of age or younger. A primary carcinoma of the stomach (16 cases) or colon (four cases) was found in 20 (90.9%) of 22 patients with available follow-up data. The primary gastrointestinal carcinomas had been diagnosed before emergence of the ovarian tumors in only five cases. The ovarian and gastrointestinal tumors were synchronously diagnosed in ten cases, while in five instances the primary carcinomas were not discovered until after the ovarian tumors had been treated. An acceptable primary extraovarian cancer was not detected in two women. Both had bilateral Krukenberg tumors and died with widespread carcinomatosis less than two years postoperatively. Typically, the ovarian tumors were bilateral, asymmetrically large and solid. Important histologic features included a greater abundance of intracellular neutral glycoproteins than acidic mucins, a storiform pattern of hyperplastic cortical stromal cells (44.4%) and carcinomatous emboli (51.6%). While the entity of "primary" Krukenberg tumor cannot be unequivocally denied, all women with typical Krukenberg tumors should be considered as having metastatic carcinoma, usually from the stomach, until proven otherwise.     

Biochemical and immunological characterizations of antigens recognised by human monoclonal antibodies

The lymphocytes from lymph nodes of six patients with metastatic mammary carcinomas were hybridised by fusion with a non-secreting variant of murine myeloma cells. Hybrid cells producing human immunoglobulin were detected by screening of culture supernatants using a solid-phase enzyme-linked immunosorbent assay for human IgG or IgM. Reactivity of human immunoglobulins to breast tumour cells was assessed by an indirect immunoperoxidase staining of fresh-frozen breast carcinoma sections. In the initial screening, the tissues used were those removed from the patients who acted as source of lymphocytes for fusion. The hybrid-cells, after repeated cloning, were stable for secretion of immunoglobulins. A total of 14 immunoglobulin G and 51 immunoglobulin M human monoclonal antibodies, showing variable reactivity to mammary carcinoma cells in tissue sections by an indirect immunoperoxidase staining method, were obtained. Two immunoglobulin G monoclonal antibodies (designated HMA-29 and HMA-31) were selected on the basis of their strong reactivity to the tumour cells and utilised to identify their corresponding antigens. The antibodies quantitatively discriminated, as expressed by the degree of staining, malignant from normal or benign mammary epithelia in freshly frozen or formalin-fixed breast tissues. The antibodies also showed reactivity to malignant cells of colon, stomach and lung and to normal cells lining the renal tubules and surface epithelium of colon. As revealed by blocking experiments, the epitopes recognised by these antibodies were not expressed on carcinoembryonic antigens, erythrocytes, lymphocytes, glycoproteins from milk-fat-globule membrane or keratins. The antibody HMA-29 immunoprecipitated a phosphoprotein (Mr = 29,000), and antibody HMA-31 two protein components (Mr = 31,000 and 34,000), from lysates of intrinsically labelled human mammary carcinoma cell line (MCF7). Neither of these proteins were present in detectable amounts in an intrinsically labelled melanoma cell line. Immunoblocking and immunoprecipitation experiments suggested that epitopes recognised by these two antibodies are dissimilar and are expressed on different molecules. The antibodies appear to be useful for functional characterisation of those antigens which are present in elevated levels in malignant compared with normal mammary epithelia.     

膜联蛋白Ⅰ在多种癌组织中的表达

目的检测分析多种癌组织中膜联蛋白(annexin)Ⅰ的表达情况,探讨其表达变化规律与不同器官的相同和不同组织学类型癌的发生发展的相关性。方法构建的628例癌组织芯片中,食管鳞癌208例,其他14种器官的相同或不同组织学类型癌组织420例。以相应正常组织作对照。用免疫组化方法检测annexinⅠ的表达情况。结果annexinⅠ在多器官(食管、肺、喉、宫颈)的鳞癌表达下降,分化差者表达更低;在多种腺癌(胃和结直肠腺癌、胰腺导管腺癌、甲状腺乳头状癌和肾透明细胞癌)中表达上调,分化差者表达更高。结论annexinⅠ在多种癌组织中的表达有明显差异,并与组织学类型和分化程度明显相关。annexinⅠ在多种癌的发生中可能有重要作用。     

Marker profile of mesothelial cells versus ovarian carcinoma cells

We investigated the marker profile of human ascitic and cultured mesothelial cells, and compared it to that of ovarian carcinoma cells which are related in terms of their histogenesis, unrelated colon carcinomas being used as reference. Mesothelial and ovarian carcinoma cells could not be distinguished by (intermediate) filament typing, using monoclonal antibodies (MAbs) to keratins, vimentins and desmins. Colon carcinomas differed from mesothelial cells and ovarian carcinomas by the absence of keratin-7 filaments. The epithelial marker BW 495/36 was completely negative on mesothelial cells and positive on all ovarian and colon carcinoma cells. While CEA was found on about 85% of all colon carcinomas, CEA expression on mesothelial cells and ovarian carcinoma cells was below 20%. The ovarian carcinoma markers (OV-TL 3, OV-TL 10, OC 125, MOV 18) were strongly positive on ovarian carcinomas and negative on colon carcinomas (or limited to traces of immunofluorescence on some samples). Although the mesothelial cells showed weak or negative reactivity with these markers, OC 125 antigen was found by immunoelectron microscopy on the surface of cultured mesothelial cells, and was shed in the culture supernatant at concentrations of 50, 28, and 25 CA 125 U/ml/10(4) positive cells. This suggests that mesothelial cells may be responsible for the synthesis of CA 125 in ascitic fluid. The data indicate that ovarian carcinomas, mesothelial cells and colon carcinomas can be distinguished using a combination of anti-keratin antibodies with BW 495/36 and anti-ovarian carcinoma markers.     

Monoclonal antibodies to human colon and colorectal carcinoma

A series of monoclonal antibodies was produced by immunizing mice with fresh carcinoma of the colon and with the cell line HT-29. These antibodies could be classified into 3 different groups: (a) those which were HT-29 specific and reacted with no other cell line or fresh colon carcinoma samples; (b) antibodies which reacted with HT-29 and were also reactive with a number of other in vitro cell lines; and (c) antibodies which appeared to be specific for carcinoma of the colon cell lines in that they reacted selectively with colon carcinoma cell lines and not with carcinoma lines derived from other tissues. It was clearly shown by immunoperoxidase staining of both normal and neoplastic cells of the gastrointestinal mucosa, from stomach to colon, that these antibodies were not tumour-specific. Indeed, one antibody (250-30.6) has a remarkable specificity for secretory epithelium of any tissue whether it be found in the gastrointestinal tract, respiratory system or urinary system. We question the existence of tumour-specific antigens detected by monoclonal antisera described thus far, and comment on the remarkable specificity of some of the sera produced, emphasized by the secretory cell-specific antibody described herein.     

尿嘧啶核苷磷酸化酶基因在胃癌、肺癌和结肠癌组织中的表达水平及其临床意义

目的分析尿嘧啶核苷磷酸化酶基因的表达水平与胃癌、肺癌和结肠癌临床病理因素之间的关系.方法采用RT-PCR法检测了28例胃癌,12例肺癌和20例结肠癌组织中尿嘧啶核苷磷酸化酶基因(UPase)的表达.结果与正常组织相比,UPase基因在胃癌组织中的表达水平增高,而在肺癌和结肠癌组织中的表达无明显差异.胃癌组织中UPase基因表达增高患者的生存率较表达正常或降低患者的生存率稍高,但无统计学意义(P＞0.05);肺癌和结肠癌组织中UPase基因表达增高患者的生存率与表达降低患者的生存率相比无明显差异(P＞0.05).UPase基因表达水平与胃癌、肺癌和结肠癌的临床期别、病理分级、淋巴结转移无相关性.结论UPase基因在胃癌、肺癌、结肠癌中表达水平不同,在胃癌组织中呈高表达状态,其高表达可能与胃癌患者的高生存率有关.     

Carcinoma of the nasal vestibule

Squamous cell carcinomas of the nasal vestibule are essentially skin cancers that require special therapeutic considerations because of the regional anatomy. They have sometimes been considered poorly suited for treatment by irradiation because of potential or actual cartilage and/or bone invasion and therefore have been treated by surgical resection, sometimes producing defects that are difficult to reconstruct satisfactorily. From 1966 to April 1980, 13 patients with squamous cell carcinoma of the nasal vestibule were treated with radiotherapy at the University of Florida. Eight lesions were de novo; 5 were recurrent after 1 or more surgical procedures. Treatment consisted of radium needle implantation and/or external beam therapy. Neck management was individualized. All de novo and 4 of 5 recurrent lesions were controlled locally. Cosmetic results were good in patients with de novo lesions. There were no instances of significant cartilage or soft tissue necrosis despite cartilage involvement by tumor in 6 cases.