An evaluation of ovarian carcinoma-associated antigen defined by murine monoclonal antibody CF511 in sera from patients with ovarian carcinoma

Murine monoclonal antibody CF511, raised against human ovarian clear cell carcinoma, detects a glycoprotein (Mr 600 kDa) called CF511 antigen which is elevated in the serum of many patients with ovarian carcinoma. A competitive enzyme-linked immunosorbent assay was developed to detect CF511 antigen in human serum and used to detected CF511 antigen in subjects with ovarian carcinoma and other diseases. No raised levels (less than 18 unit (U) ml-1) of the antigen were found in the serum of 220 normal individuals or of patients with germ cell tumours (n = 6), granulosa theca cell tumour (n = 1), gastric carcinomas (n = 10) and colo-rectal carcinomas (n = 8). Raised serum levels of CF511 antigen were found in 6/46 patients (13.0%) with benign gynaecological tumours (including endometriosis or ovarian cyst), in 5/7 patients (71.4%) with breast carcinoma and 16/21 (76.2%) lung carcinoma patients. In patients with ovarian carcinoma, 42.3% (11/26) of stage I and II, and 96.0% (24/25) of stage III and IV had levels of greater than or equal to 18 U ml-1. In all patients with serial determination of CF511 antigen levels before and after the surgery, the levels of antigen correlated with the clinical course of disease. Determination of CF511 antigen levels may be useful for detection of ovarian carcinoma as well as lung and breast carcinomas and for monitoring progress of disease and response to therapy.     

Identification of two different surface epitopes of human ovarian epithelial carcinomas by monoclonal antibodies

Monoclonal antibodies (Mabs) against human ovarian mucinous and serous carcinoma were obtained by the Mab technique. Their reactivities against human tumors were tested by indirect immunofluorescence. One of the Mabs, named 4C7, derived from the spleen cells of mice immunized with mucinous carcinoma line OVA-1, reacted to ovarian mucinous carcinoma, endometrioid carcinoma, and mesonephroid carcinoma but did not react to ovarian serous carcinoma. Another Mab, 3C2, obtained from the spleen cells of mice immunized with serous carcinoma line HOC-21, reacted to serous carcinoma and endometrioid carcinoma of ovary, but never reacted to mucinous carcinoma or mesonephroid carcinoma. Neither of the Mabs reacted to other types of ovarian carcinomas such as undifferentiated carcinoma, dysgerminoma, endodermal sinus tumor, and malignant teratoma of ovary, and also did not react to any benign ovarian tumors or other normal human tissues. Both Mabs 3C2 and 4C7 had no reactivity to carcinoma of other organs such as stomach, colon, lung, lymphoid system, and kidney and also did not react to human lymphocytic or carcinoembryonic antigen as confirmed by using many human cell lines and surgically resected samples. Since the cross-reactivities of these Mabs were limited within the ovarian epithelial carcinomas, it is suggested that two distinct epitopes are expressed on the ovarian epithelial carcinomas. One epitope, identified by Mab 4C7, is expressed only on mucinous carcinoma, endometrioid carcinoma, and mesonephroid carcinoma, while the epitope, identified by Mab 3C2, appears only on serous and endometrioid carcinoma.     

Comparative analysis of CA125, tissue polypeptide specific antigen,and soluble interleukin-2 receptor alpha levels in sera,cyst, and ascitic fluids from patients with ovarian carcinoma

BACKGROUND: The serum markers CA125, tissue polypeptide specific antigen (TPS), and soluble interleukin-2 receptor alpha (sIL-2Ralpha) concentrations were determined in sera, cyst, and ascitic fluids from patients with malignant and benign ovarian neoplasms. METHODS: CA125, TPS, and sIL-2Ralpha concentrations were measured in sera, cyst, and ascitic fluids by immunoassays in 67 patients with carcinoma and in 32 patients with benign ovarian neoplasms. RESULTS: CA125, TPS, and sIL-2Ralpha levels were elevated significantly in sera from patients who had ovarian carcinoma compared with patients who had benign neoplasms (P < 0.001). Patients who had International Federation of Gynecology and Obstetrics (FIGO) Stage III-IV disease had significantly higher serum levels for the markers studied compared with patients who had FIGO Stage I-II disease (P < 0.001 for CA125; P = 0.02 for TPS and sIL-2Ralpha). Concurrent measurement of CA125 and sIL-2Ralpha in sera identified 100% of ovarian carcinomas in FIGO Stage I-II. All patients with carcinoma demonstrated markedly higher levels of CA125 and TPS for both cyst and ascites compared with corresponding sera (P < 0.001). The level of sIL-2Ralpha was higher statistically in ascitic fluid compared with the level in serum (P < 0.001); however, its values in sera and cyst fluids were comparable. In ascitic fluid, the CA125 level was significantly higher in patients who had FIGO Stage III-IV disease compared with patients who had FIGO Stage I-II disease (P = 0.002), whereas such correlations were not found for TPS or sIL-2Ralpha. In cyst fluids, the levels of all studied markers were independent of the FIGO stage. In cyst fluids from patients with benign ovarian neoplasms, TPS and sIL-2Ralpha levels were significantly lower compared with the levels in patients with ovarian carcinoma (P < 0.001), whereas the values of CA125 were overlapping. CA125 and TPS concentrations were higher in cyst fluids compared with corresponding sera, whereas sIL-2Ralpha levels were comparable and low in cyst fluids and in the circulation of patients with benign neoplasms. CONCLUSIONS: In patients with ovarian carcinoma, TPS and CA125 concentrations were significantly higher in the place of their generation compared with the concentrations in blood circulation. sIL-2Ralpha values were higher in ascites compared with the values in corresponding sera, and its concentrations in sera and cyst fluids were comparable. The assessment of serum sIL-2Ralpha levels showed potential complementary value to CA125 for the detection of ovarian carcinoma in early FIGO stages; however, a 9% false positive rate limited the significance of cumulative value for a combination of these circulating markers.     

Elevated levels of a high molecular weight antigen detected by antibody W1 in sera from breast cancer patients

A novel screening assay was used to test 13 previously described antibreast cancer antibodies for those which recognize antigens elevated in serum of breast cancer patients. Binding of three of these antibodies to breast or lung carcinoma cells was inhibited to a significantly greater extent by tumor patient serum than by normal serum, suggesting that the antigens might be useful serum markers. Two of these antibodies, W1 and W9, were shown to recognize nonoverlapping epitopes on a high molecular weight molecule(s) purified from serum from breast cancer patients. A sensitive double determinant immunoassay was developed to measure W1 antigen levels in sera from a total of 389 cancer patients and controls. Forty seven % (37 of 79) of individuals having breast cancer showed elevated serum levels of the W1 antigen, whereas only 4% (1 of 25) of normal controls and 2% (1 of 47) of patients hospitalized for nonmalignant disorders showed elevated levels. These differences were statistically significant (P less than 0.001). The percentage of breast cancer patients showing elevated serum levels was greater for individuals with metastatic disease. Statistically significant numbers of lung, ovarian, and prostate, but not colon, cancer patients also had elevated serum levels of the W1 antigen. These data suggest that measurement of the W1 antigen in serum might provide clinically useful information on the course of metastatic breast and other cancers.     

Monoclonal antibodies reactive with the breast carcinoma-associated mucin core protein repeat sequence peptide also recognise the ovarian carcinoma-associated sebaceous gland antigen.

The monoclonal antibody (Mab) OM-1, which defines the ovarian carcinoma-associated sebaceous gland antigen (SGA), and Mab F36/22, which defines the ductal carcinoma antigen (DCA), were tested for reactivity against a synthetic peptide representing the repeat twenty amino acid sequence of the human polymorphic epithelial mucin core protein plus four amino acids of the adjacent sequence (p1-24). OM-1 bound strongly to the peptide by direct dot blot assay and ELISA and the minimum epitope for OM-1 was shown to be APDTRP(A) by inhibition assay. F36/22 reacted weakly with the peptide under the same conditions and its affinity for peptide in solution was relatively very low. Mab OC125, which defines the ovarian cancer-associated antigen CA125, did not react with the p1-24 peptide. Five other anti-mucin Mabs (HMFG1, HMFG2, BC1, BC2, BC3), previously shown to bind to the p1-24 peptide, reacted strongly with SGA by direct binding and in a sandwich assay with OM-1 as the capture Mab. F36/22 was weakly positive under the same conditions suggesting that both peptide and SGA do not express the optimal epitope for F36/22 binding. These results indicate that SGA and possibly DCA have the repeat sequence core protein of the breast carcinoma-associated human polymorphic epithelial mucin.     

Distribution of lung adenocarcinoma-associated antigens in human tissues and sera defined by monoclonal antibodies KM-52 and KM-93

Two monoclonal antibodies to human lung adenocarcinoma, KM-52 and KM-93, were generated by the novel immunizing procedure using mice rendered tolerant to the normal human lung (N. Hanai et al., Cancer Res., 46: 4438-4443, 1986). KM-93 recognized sialylated carbohydrate epitope on the antigen different from CA19-9 and DU-PAN-2, while KM-52 recognized the protein antigen. Both antigens were different from carcinoembryonic antigen, alpha-fetoprotein, and beta 2-microglobulin. Distribution of KA-52 and KA-93, the antigens recognized by KM-52 and KM-93, respectively, in various tissues and sera was investigated. In immunoperoxidase staining, KM-93 reacted strongly and frequently with tumor cells of lung adenocarcinoma and partially with those of lung squamous cell carcinoma, large cell carcinoma, and small cell carcinoma. In normal adult and fetal tissues, KA-93 was expressed on the surface of a small number of cells of the lung, pancreas, liver, kidney, and bone marrow. KM-52 reacted selectively with tumor cells of adenocarcinoma among four different histological types of lung carcinoma. In normal adult and fetal tissues, KA-52 was distributed on a small number of cells of the lung, stomach, intestine, and pancreas. Of the two monoclonal antibodies, KM-93 could be used in detecting the antigen in sera of patients with lung cancer. The KA-93 level in sera was determined by the sandwich-type enzyme-linked immunosorbent assay. Serum with a high KA-93 level was found in 34 of 70 patients with lung adenocarcinoma (48.6%), one of 67 healthy adults (1.5%), and none of 32 patients with benign diseases (0%). Combined detection by KA-93 with KA-32, a new tumor marker of lung squamous cell carcinoma (N. Hanai et al., Cancer Res., 46: 5206-5210, 1986), elevated the positive percentage in patients with lung squamous cell carcinoma (52.7%) and with lung adenocarcinoma (59.5%). These results suggested that KM-52 and KM-93 would be potential monoclonal antibodies in immunohistological diagnosis and serum diagnosis of lung adenocarcinoma, respectively.     

Fucosylated type-2 chain polylactosamine antigens in human lung cancer

Four specific monoclonal antibodies (MAbs) have been used to study distributions of fucosylated type-2 chain polylactosamine antigens, Lex, poly Lex, Ley and sialylated Lex-i antigens, in human lung cancer tissues and in the serum of patients with lung cancers. Radioimmunoassay frequently showed abnormally high antigen levels in the sera of 66 lung cancer patients tested. When histological typing was performed, high serum levels of the above 4 antigens were most frequently observed in patients with adenocarcinoma of the lung; i.e., after combining the results from the 4 antigens, 75% of the sera from patients with lung adenocarcinoma were positive (50% in the case of large-cell carcinoma, 30% in the case of squamous-cell carcinoma and 27% for small-cell carcinoma). Among the 4 antigens, the sialylated Lex-i antigen had the highest positive incidence, 58%, in the sera of patients with adenocarcinoma of the lung, compared to 33% for Ley, 29% for poly Lex, and 8% for Lex antigen. On the other hand, when the distributions of these antigens in the lung cancer tissues of 42 patients were studied by immunohistological techniques, the Ley antigen had the highest positive incidence, 100%, in lung adenocarcinoma tissues, poly Lex antigen had 86%, sialylated Lex-i antigen had 71%, and Lex antigen had 29%. In cancer tissues, the incidence of non-sialylated antigens, such as Ley, poly Lex and Lex antigens, often exceeds the positive incidence of the sialylated antigen, but the sialylated form of the antigen, such as sialylated Lex-i antigen, appears more often than the non-sialylated form in patients' sera.     

卵巢上皮癌的预后影响因素分析

目的:探讨卵巢上皮癌预后的影响因素.方法:回顾分析自2005年1月至2010年12月在陕西省肿瘤医院收治的292例卵巢上皮癌患者的临床资料.采用Kaplan-Meier法分析生存时间,应用Log-rank法进行组别间生存率差异检验,采用OR值对各因素间进行危险度分析.结果:年龄、手术分期、组织学类型、病理分化程度、肿瘤细胞减灭术后残余瘤的大小以及术后化疗疗程数是卵巢上皮癌的预后生存指标.以FIGOⅠ期患者的死亡风险为1,则Ⅱ期、Ⅲ期、Ⅴ期的死亡风险分别为Ⅰ期的3倍、14.7倍、21.8倍;以术后残余瘤直径≤2cm患者的死亡风险为l,则残余瘤直径＞2cm的患者的死亡风险为残余瘤直径≤2cm患者的死亡风险的80.7倍;化疗疗程数＜6疗程的死亡风险为≥6疗程的2.3倍.以高分化患者的死亡风险为l,则中、低分化的死亡风险分别为高分化的2.4倍、3.8倍.结论:FIGO分期,首次肿瘤细胞减灭术后残余瘤的大小、化疗疗程数、病理分化程度是卵巢上皮癌的独立预后因素.因此尽力做到早诊断、早治疗,术后辅以正规、足程的化疗是提高卵巢上皮癌生存率的关键.     

Hepsin在卵巢癌组织中表达与临床病理意义

目的 探讨Hepsin蛋白表达与卵巢癌临床病理相关性。方法 采用免疫组化方法检测正常卵巢20例、卵巢良性肿瘤25例和卵巢癌139例中Hepsin蛋白表达情况。采用统计学方法分析Hepsin蛋白表达与临床病理的关系。结果 所有卵巢癌样本中有90例(64.7%)Hepsin高表达,正常卵巢和卵巢良性肿瘤均未见明显表达或弱表达。FIGO分期越晚,Hepsin蛋白表达程度越高;组织分化程度与Hepsin蛋白表达程度呈正相关,即组织分化越差,Hepsin蛋白表达量越高。结论 Hepsin蛋白的表达与卵巢癌上皮癌的临床分期和组织分化程度密切相关,Hepsin蛋白表达与临床分期呈正比,而与组织分化程度成反比。Hepsin蛋白异常表达可能是促进卵巢癌发生发展的重要机制。     

Epitope analysis of monoclonal antibody NCRC-11 defined antigen isolated from human ovarian and breast carcinomas

NCRC-11 is an IgM monoclonal antibody which defines an antigen found in most epithelial malignancies. The antigen has previously been shown to be a high mol. wt. glycoprotein (greater than 400,000) and in this study, antigen preparations were isolated by immunoadsorbent chromatography from ovarian mucinous and ovarian serous cyst adenocarcinoma and from breast carcinoma. Other monoclonal antibodies, against products in normal human milk, and antibodies of the Ca series (Bramwell et al., 1985) reacted with all three antigen preparations. Tests involving epitope mapping were performed to probe the relationships of the various epitopes to that defined by the NCRC-11 antibody, and, of note, the three antigen preparations from different tumour sources were remarkably similar with respect to their relative levels of epitope expression and to their topographical distribution of epitopes. The major differences in epitope expression could be attributed to the degree of sialylation in the three antigens. The antigens from ovarian tumours expressed I(Ma) blood group determinants (defined by the antibody LICR-LON-M18) which were partially masked by sialic acid. With NCRC-11 defined antigen from breast carcinoma, this determinant was totally masked by sialic acid although neuraminidase treatment clearly exposed epitopes reactive with M18 antibodies.     

Levels of circulating tumor-associated glycoprotein (TAG-72) in patients with carcinoma using a novel tumor marker, CA 72-4

CA72-4 is a novel quantitative immunoradiometric assay system utilizing two monoclonal antibodies CC-49 and B72.3, which recognize a tumor-associated glycoprotein (TAG-72). We have utilized the CA72-4 RIA kit to measure serum levels of TAG-72 in 205 patients with carcinoma and 192 patients without carcinoma. The cut-off value (4.0 U/ml) was obtained according to the levels and the distribution of CA72-4 in 468 healthy individuals. The positive rates in 82 patients with gastric cancer, 55 with colorectal cancer, 24 with pancreatico-choledochal cancer, 36 with breast cancer, and 3 with ovarian cancer were 52%, 55%, 46%, 39%, and 67%, respectively. Fifty percent of the sera from 205 patients with carcinoma demonstrated increased levels of CA72-4, whereas only 10% of the sera from 192 patients without evidence of malignancy showed levels more than 4.0 U/ml. The average level of serum CA72-4 in the patients with carcinoma was 38.6 U/ml, much higher than that (2.7 U/ml) in patients without malignancy. The patients with gastrointestinal cancer at advanced stages or at recurrence showed higher levels of serum CA72-4 than the patients with cancer at early stages. These results thus indicate that CA72-4 is clinically useful as a novel tumor marker, especially for monitoring serum levels of TAG-72 in patients with gastrointestinal cancer, breast cancer, ovarian cancer and other epithelial malignancies.     

Evaluation of MSA as a serum marker in breast cancer: a comparison with CEA

In a blind study, 518 serum samples were assayed for serum levels of mammary serum antigen (MSA) by an enzyme immunoassay (EIA) using the 3E1.2 monoclonal antibody. Using 300 IU as the arbitrary cut off to distinguish normal from abnormal individuals, 75% of patients with primary Stage I carcinoma of the breast (n = 12), 89% of those with Stage II (n = 9) and 93% of those with Stage IV (n = 57) had elevated levels of MSA. A relationship was observed between the level of MSA and stage of disease, and therefore with the extent of tumour burden. Levels of MSA were also determined in a series of 19 patients undergoing chemotherapy for breast cancer. Over a 2-24 month period, the change of MSA levels corresponded with the clinical course of the disease in 17 (89%) cases. MSA levels were also raised in some patients with ovarian, colon, lung and kidney cancer, but the average level was lower than in patients with breast cancer. A comparison of CEA and MSA levels in these patients revealed that MSA was a substantially better marker for breast cancer than CEA. The results of this study demonstrate that MSA levels are elevated in patients with breast cancer and may provide a useful means of following the clinical course of patients with this disease.     

Analysis of human ovarian tumor antigens using heterologous antisera: detection of new antigenic systems.

Rabbits were immunized with extracts of human ovarian cystadenocarcinomas in an attempt to identify the spectrum of ovarian tumor antigens recognizable by heteroimmune sera. After absorption, the reactivity of the sera with extracts of tumors and normal tissues was examined by double diffusion in agar. Six antigens (OvC-1, 2, 3, 4, 5 and 6), which could not be detected in normal ovary, were found in a variable proportion of ovarian tumors. Two of these antigens (OvC-4 and 5) proved to be previously recognized tissue antigens, carcinoembryonic antigen (CEA) and the related normal glycoprotein (NGP). A third antigen (OvC-3) was shown to be identical to pregnancy-zone protein (PZP, SP₃, PAG). It was detected in 20 of 93 epithelial cancers of the ovary and in 20 of 22 sera from ovarian cancer patients. OvC-6 was an individually specific antigen detectable only in the immunizing tumor. OvC-1 and OvC-2 are unrelated to well-defined tumor antigens. The former was detectable in 48 of 93 epithelial cancers of the ovary, in some cervical, breast, gastric and pancreatic cancers and also in normal kidney and lung. Its presence in cord and pregnancy sera, and in placenta and amniotic fluid, indicates that it may be a new pregnancy-associated protein. OvC-2 is confined to ovarian cancers (8/93) and cannot be detected in tumors of other types or in normal adult tissues. Since it is present in placenta, amniotic fluid and fetal intestine it can be considered to be a fetal or differentiation antigen.     

Distribution of oncofetal antigen tumor-associated glycoprotein-72 defined by monoclonal antibody B72.3

Murine monoclonal antibody B72.3, prepared against a membrane-enriched extract of human metastatic carcinoma, was reacted with a spectrum of adult and fetal human tissues using avidin-biotin-complex immunohistochemical techniques to evaluate the expression of the reactive tumor associated glycoprotein (TAG)-72 antigen. TAG-72 was shown to be expressed in several epithelial-derived cancers including 94% of colonic adenocarcinomas, 84% of invasive ductal carcinomas of the breast, 96% of non-small cell lung carcinomas, 100% of common epithelial ovarian carcinomas, as well as the majority of pancreatic, gastric, and esophageal cancers evaluated. TAG-72 expression was not observed, however, in tumors of neural, hematopoietic, or sarcomatous derivation, suggesting that the TAG-72 antigen is "pancarcinoma" in nature. Appreciable monoclonal antibody B72.3 reactivity was generally not observed in adult normal tissues, with limited reactivity noted in a few benign lesions of the breast and colon. TAG-72 antigen expression was detected, however, in fetal colon, stomach, and esophagus, thus defining TAG-72 as an oncofetal antigen. TAG-72 has previously been shown to be distinct from carcinoembryonic antigen and other tumor associated antigens. The pancarcinoma distribution and lack of significant reactivity with normal adult tissues of monoclonal antibody B72.3 suggest its potential diagnostic and therapeutic utility for human carcinomas.     

MAM-6 antigen, a new serum marker for breast cancer monitoring

Almost all carcinomas contain a cell surface antigen, MAM-6, which has been defined by several monoclonal antibodies, including 115D8 (Hilkens et al., Int. J. Cancer, 34: 197-206, 1984). A quantitative sandwich radioimmunoassay, using 115D8 as catcher and as tracer antibody, has been developed to detect MAM-6 in serum. To quantitate the MAM-6 level, pooled human milk was used as a standard, and arbitrary units were chosen. Less than 5% of the sera of apparently healthy individuals contained more than 5 units/ml. In sera of patients with benign breast lesions, the same low levels were detected. However, concentrations over 5 units/ml were found in 24, 21, 43, and 79% of the sera of patients with pathological Stages I, II, III, and IV breast cancer, respectively. MAM-6 levels were also increased in almost all sera tested from patients with advanced stages of ovarian carcinoma, but in a low percentage of sera from patients with other advanced cancers. A longitudinal study was carried out to test the MAM-6 assay as clinical marker to monitor the therapeutic response of breast cancer. Increasing or decreasing MAM-6 serum levels correlated in 93% of the cases with breast cancer progression or regression, indicating that the assay can be used to monitor the course of the disease during therapy. In some breast cancer patients, elevated MAM-6 levels were observed prior to any clinical indication of tumor recurrence.     

Detection of C-ERBB-2 Related Protein in Sera from Breast Cancer Patients Relationship to ERBB2 gene amplification and c-erbB-2 protein overexpression in tumour

The level of a c-erbB-2 related protein was determined in sera from 168 breast carcinoma patients, 12 females with benign breast disease, and 66 female controls using an ELISA (enzyme linked immunosorbent assay) kit. Elevated c-erbB-2 related protein level was detected in one of 13 preoperative sera (8%), two of 62 postoperative sera from patients without recurrent disease (3%), and 55 of 93 sera collected at recurrent disease (59%). Elevated serum levels were detected significantly more often in patients with distant metastases than in patients with recurrent disease restricted to locoregional areas (68% versus 19%). Presence of elevated serum level was associated with ERBB2 gene amplification and c-erbB-2 protein overexpression in tumour. None of the patients who had normal ERBB2 gene copy number in tumour had elevated serum levels. Although the usefulness in postoperative prediction of the presence of micrometastases is somewhat questionable, the results suggest c-erbB-2 related protein to represent a novel tumour marker in serum and other body fluids from breast cancer patients at the time of diagnosis and during treatment monitoring.     

LRP与c-erbB-2在上皮性卵巢癌中的表达及临床意义

目的探讨肺耐药蛋白(lungresistanceprotein,LRP)与c-erbB-2在上皮性卵巢癌中的表达及其临床意义。方法采用免疫组织化学SP法检测108例上皮性卵巢癌组织和10例正常卵巢组织中LRP和c-erbB-2的表达,并进行相关的临床病理参数分析。结果LRP和c-erbB-2在上皮性卵巢癌中的阳性表达率分别为70.4%和64.8%,而正常卵巢组织中均未见表达,两者表达差异均有显著性(P<0.05)。上皮性卵巢癌组织中LRP的表达与上皮性卵巢癌组织学类型、临床分期、病理分级、患者年龄、残留病灶等临床病理参数无关。c-erbB-2的表达与组织学类型、临床分期、患者年龄和残留病灶无关,与病理分级有关(P<0.05)。LRP表达阳性的卵巢癌患者对化疗的反应率(44.7%)明显低于LRP表达阴性者(93.7%)(P<0.05);c-erbB-2表达阳性的卵巢癌患者对化疗的反应率(42.8%)明显低于c-erbB-2表达阴性者(89.4%)(P<0.05)。结论LRP和c-erbB-2在上皮性卵巢癌中有较恒定的表达,且阳性表达预示化疗反应率低,可能成为预测卵巢癌化疗耐药的指标。     

Comparative diagnostic aspects of herpes simplex virus tumor-associated antigens.

Sera from cancer patients and healthy individuals, obtained from two independent sources, were examined for their abilities to react with herpes simplex virus-associated tumor antigens, AG-4 and NVA-TAA (nonvirion antigen-tumor-associated antigen). Both antigens were prepared by infection of HEp-2 cells with herpes simplex virus type 2, and all antigen-antibody interactions were measured by the micro-complement fixation test. Of sera from 16 patients with cancer of the uterine cervix, 81% (P less than 0.01) reacted with NVA-TAA, whereas 78% (P less than 0.001) of 18 sera examined reacted with AG-4. These values differed significantly from those for normal sera, of which 14% reacted with NVA-TAA and 13% with AG-4. Of sera for 8 patients with squamous cell carcinoma of head and neck or vulva, 75% (P less than 0.02) reacted with NVA-TAA, whereas 63% (P less than 0.05) reacted with AG-4. As a group, other cancers (including adenocarcinoma of lung, breast, ovary, and cervix; liposarcoma; sarcoma; melanoma; and carcinoma of the endometrium) did not differ significantly from controls in reactive patterns with AG-4 or NVA-TAA. These studies partly supported the reported preferential reactivity of AG-4 and NVA-TAA with sera of patients with squamous cell carcinoma, especially of the uterine cervix.     

Circulating CA 15-3 antigen levels in non-mammary malignancies

Abnormal CA 15-3 antigen levels are found in the serum of most patients with advanced breast carcinoma. Elevations of this marker are less frequently seen in other malignancies. Circulating CA 15-3 levels might be useful in the differential diagnosis of the primary site of cancer. We studied the levels of CA 15-3 in 500 patients with different non-mammary cancers. Elevations of CA 15-3 (greater than 40 U ml-1) were observed in all types of epithelial malignancies, especially in ovarian (46%), respiratory (26%) and liver (30%) carcinomas. Abnormal values were observed in some patients with haematological malignancies and sarcomas, but not in melanoma or neurological tumours. CA 15-3 antigen levels correlated with the extent of non-mammary malignant tumours. Patients with locoregional cancer had a significantly smaller proportion of elevations of the antigen than those with distant metastases (12% versus 35%, P less than 0.001). In particular, elevated CA 15-3 levels were observed in 70% of patients with metastatic ovarian cancer. Liver involvement by cancer did not produce more elevations of CA 15-3 than metastases to other organs (32% versus 39%). Simultaneous determination of circulating CA 15-3 and CA 125 antigens in 58 patients with cancer of the ovary showed that CA 15-3 is elevated in some cases of ovarian carcinoma with non-elevated CA 125, and that CA 15-3 and CA 125 are distinct antigens. We conclude that circulating CA 15-3 antigen levels can be found elevated in virtually all types of cancer, particularly when distant metastases are present. Therefore, CA 15-3 levels should not be used in the differential diagnosis of the primary site in patients with metastatic malignancies of unknown origin. Evaluation of CA 15-3 levels may enhance the sensitivity of CA 125 in monitoring the course of ovarian carcinoma.     

PKP4在卵巢上皮性浆液性囊腺癌组织中的表达及其临床意义

目的:检测PKP4（plakophilin 4,又称p0071）在卵巢上皮性浆液性囊腺癌组织中的表达,探讨PKP4参与肿瘤发生发展的机制及其临床意义。方法:利用免疫组化SP法检测PKP4在55例卵巢上皮性浆液性囊腺癌,12例卵巢上皮性交界性肿瘤,13例卵巢上皮性良性肿瘤,15例正常卵巢组织中表达情况,分析其与卵巢上皮性浆液性囊腺癌患者临床病理参数及预后的关系。结果:PKP4以细胞膜、细胞质着色为主,PKP4在卵巢上皮性浆液性囊腺癌组织中阳性表达率(94.55%)明显高于正常卵巢组织(26.67%)、卵巢上皮性良性肿瘤组织(46.15%)及卵巢上皮性交界性肿瘤(75.00%)(P＜0.05)。PKP4表达随FIGO分期增加而增高(P＜0.05),是影响卵巢上皮性浆液性囊腺癌患者总生存时间和预后的独立危险因素。结论:PKP4与卵巢癌的发生、发展和预后相关,有望在卵巢癌的早期诊断及预后评估方面发挥重大意义。