Accumulation of p53 protein correlates with a poor prognosis in human lung cancer.

Mutations in the gene coding for the p53 tumor suppressor protein are common in a variety of human cancers. To assess the role of a putative mutated p53 protein in human lung cancer, a monoclonal antibody recognizing it was used in an immunoperoxidase detection system. A total of 114 cases of Stage I and II adenocarcinomas and squamous cell carcinomas were studied. The staining pattern was always intranuclear and heterogeneous. When the median or mean survival time was compared between cases, p53 accumulation had a statistically significant negative prognostic value. This was supported by a Kaplan-Meier survival plot of p53 producers and nonproducers. In 7 of 24 Stage II cases that were negative for p53 in the primary tumor, metastatic regional lymph nodes were p53-positive. These latter cases had greatly reduced survival times. Thus, p53 accumulation in primary tumors (and regional lymph nodes) may identify a subgroup of lung cancer patients with a prognosis of more aggressive disease.     

Lymphoscintigraphy of human colorectal carcinoma metastases in athymic mice by use of radioiodinated B72.3 monoclonal antibody

The potential of radioiodinated monoclonal antibody B72.3 for lymphoscintigraphy was evaluated, using suitable animal models of a human colorectal carcinoma. LS174T xenografts were grown at various sites in beta-estradiol-pretreated athymic mice, and the development of metastases in different organs was assessed histologically. After iv inoculation of the mice, 66% of the animals developed "metastases" to the axillary lymph nodes. Of these mice, 100% also developed multiple tumors on their backs and 79% had lung micrometastases. Livers, kidneys, and spleens showed no evidence of tumor growth. In 33% of the mice in which primary LS174T tumors had been removed from the hindfoot pad, metastases to the popliteal lymph nodes were observed 3 1/2 weeks after tumor implantation. BALB/c (nu/nu) female mice bearing axillary and popliteal lymph node metastases were used to test the potential of radiolabeled B72.3 antibody (an IgG1) as a lymphoscintigraphic agent. A monoclonal antibody against horseradish peroxidase (also an IgG1), which did not bind LS174T tumor cells in vitro, served as a control. Both normal and tumor-bearing axillary and popliteal lymph nodes imaged up to 6 hours after the sc injection of 20-40 mu Ci of 125I-labeled B72.3 into either the forefoot or hindfoot pads. The localization index (L.I.) (specific/nonspecific antibody in tumor divided by specific/nonspecific antibody in blood) for LS174T tumors in lymph nodes was approximately 1 during the first 6 hours after antibody injection, thus indicating no specific antibody accumulation. Twenty-four hours and later after sc injection, images of nodal metastases (14-477 mg) and specific antibody accumulations were observed. At these times the L.I.'s ranged 1.5-3.5. Tumor-negative nodes did not image at 24 hours after injection of 125I-labeled B72.3. The L.I.'s of the normal nodes and of other tissues from these mice were about 1.0 at 24 hours, indicating no specific antibody accumulation. Autoradiographic analysis of lymph nodes containing LS174T tumor showed heterogeneous antibody distribution of B72.3 within tumor sections with heavy patches of antibody accumulation in mucin globules. In lymph nodes the normal lymphocytes adjacent to the LS174T tumor cells showed no antibody accumulation. The lack of specific, early antibody accumulation by LS174T tumor-bearing nodes in mice suggests that B72.3 does not accumulate in nodal metastases to the degree necessary to consider it a potential agent for use in lymphoscintigraphy.     

Disseminated tumor cells in lymph nodes as a determinant for survival in surgically resected non-small-cell lung cancer.

PURPOSE: In recent years, the detection of even a few tumor cells in lymph nodes of patients with surgically resected non-small-cell lung cancer (NSCLC) became possible with immunohistochemical staining procedures. Tumor cells in lymph nodes have been shown to be associated with an increased rate of early recurrence. However, the prognostic significance of this minimal tumor cell spread for overall survival remains unclear. PATIENTS AND METHODS: We used the epithelium-specific monoclonal antibody Ber-EP4, which recognizes the 17-1A antigen (also called EGP40 or Ep-CAM), to discover small tumor cell deposits (< or = three cells) in 565 regional lymph nodes judged as tumor-free by conventional histopathology in patients with NSCLC staged as pT1-4, pN0-2, M0, R0. In a prospective analysis, we studied the influence of the detected tumor cells on the cancer recurrence rate and survival of 117 patients. RESULTS: Ber-EP4-positive cells were found in 27 of 125 patients (21.6%). After an observation period of 64 months, patients with disseminated tumor cells had reduced disease-free survival (P < .0001) and overall survival (P = .0001) rates in univariate analyses (logrank test). Multivariate analysis (Cox model) showed a 2.7 times increased risk for tumor relapse and a 2.5 times increased risk for shorter survival in patients with disseminated tumor cells compared with patients without such cells. Patients without any evidence of histopathologic and immunohistochemical lymph node involvement had an overall survival rate of 78%. CONCLUSION: The immunohistochemical detection of disseminated tumor cells in lymph nodes of patients with completely resected NSCLC is an independent prognostic factor for overall survival.     

Malignant potential and cytogenetic characteristics of occult disseminated tumor cells in esophageal cancer

Although micrometastatic cancer cells in lymph nodes can be detected by monoclonal antibodies against epithelial or tumor-associated antigens, it remains unclear whether these cells are precursors of overt metastases or shedded tumor cells with a limited life span. Here we used esophageal cancer as a model to evaluate the prognostic significance and biological characteristics of such micrometastases. In lymph nodes classified as tumor free by conventional histopathological staging, tumor cells were identified with monoclonal antibody Ber-EP4 in 89 of 126 patients (71%) with completely resected (R0) esophageal carcinomas. Multivariate survival analysis underlined the strong and independent prognostic significance of Ber-EP4-positive cells in "node-negative" (pN0) patients. To assess the biology of Ber-EP4-positive cells, we established tumor cell lines from an immunohistochemically positive lymph node and the autologous primary tumor. p53 mutational analysis and multiplex-fluorescence in situ hybridization revealed common aberrations shared between both cell lines, whereas an insertion of chromosome 13 material in the short arm of chromosome 1 was only observed in micrometastatic cells. The tumorigenicity and metastatic potential of both cell lines were demonstrated in severe combined immunodeficient mice. In conclusion, our data provide first direct evidence for the malignant potential of micrometastatic cancer cells.     

Increased expression of Thomsen-Friedenreich antigens during tumor progression in breast cancer patients

Paraffin-embedded tissue sections of primary tumors and lymph node metastases of 80 breast cancer patients were tested for the expression of Thomsen-Friedenreich (TF) antigens with the aid of a monoclonal IgM antibody (49H8) highly specific for phenyl-beta-galactoside. TF antigens were not expressed in 16 different normal tissues with the exception of some structures in the kidney. In tumor cells, two types of antigen expression were found; namely, cryptic and exposed. From stage T1/No to stages T2-4/N1,2 the number of cases expressing high amounts of TF antigens increased from 9% (2/22) to 22% (4/18) while the percentage of patients with low intensity of antibody binding was reduced from 59% (13/22) to 39% (7/18). The total amount of TF-positive primary tumors at stages T2-4/No increased from 42% (8/19) to 69% (18/26) when lymph nodes were infiltrated (T2-4/N1,2). At this stage 80% (21/26) of the patients with lymph node infiltration carried TF antigens in the nodes. The distribution of antigens was heterogeneous among the tumor cells and was expressed mainly in an apical or luminal position. The increased expression of antigens was attributed to exposed TF antigens, while cryptic antigens remained constant. When primary tumors expressed exposed TF antigens, the corresponding lymph nodes also contained exposed antigen. The same was true for the cryptic antigen. The data demonstrate an increase in the intensity of TF antigen expression during tumor progression and a spread of TF-positive tumor cells into the axillary lymph nodes with an increasing number of breast cancer patients being TF-positive at this stage.     

Detection of bone marrow metastasis in small-cell lung cancer by monoclonal antibody

A murine monoclonal antibody against a surface antigen of small-cell carcinoma of the lung (SM1 antibody) was investigated for its use in detecting bone marrow metastasis. Bone marrow cells of healthy volunteers and of patients with small-cell carcinoma of the lung (SCCL) were examined for reactivity with SM1 antibody and indirect immunofluorescence and the results compared to conventional histochemical staining (Wright-Giemsa stain of bone marrow aspirates and hematoxylin-eosin stains of bone marrow biopsies). No SM1 reactivity was found in marrow cells of eight healthy volunteers. Thirty-six samples from 33 patients with SCCL were examined; tumor involvement was found in 69% by SM1 antibody and in 16% by histochemical stains. All bone marrow samples from patients with SCCL that were unreactive with SM1 antibody also showed no evidence of tumor involvement by histochemical stains. Samples of 29 patients were investigated at initial staging; SM1 reactive cells were found in 50% of 16 patients with limited disease and in 77% of 13 patients with extensive disease. Overall, the proportion of patients recognized to have disseminated disease at diagnosis was increased from 45% to 72% by monoclonal antibody staining. Indirect immunofluorescence with SM1 antibody allows detection of bone marrow metastasis of SCCL that cannot be seen by conventional morphology and can identify disseminated disease in patients otherwise staged limited disease.     

An immunohistochemical study of c-erbb-2 protein in gastric carcinomas and lymph-node metastases: Is the c-erbB-2 protein really a prognostic indicator?

An immunohistochemical study of the c-erbB-2 protein was conducted on formalin-fixed paraffin-embedded tissue sections from 136 primary gastric carcinomas and 50 metastatic lymph node tumors obtained at gastrectomy. Expression of the protein was detected in 35 of 136 primary gastric carcinomas (25.7%) and 22 of 50 metastatic lymph nodes (44%). The staining pattern of tumor cells was classified as membranous or cytoplasmic. An immunohistochemical study using serially diluted antibody demonstrated that 82.6% of positive cases in metastatic lymph nodes showed c-erbB-2 immunoreactivity stronger than that in the primary tumors. Membranous staining was stronger than cytoplasmic staining. c-erbB-2 protein of the cytoplasmic as well as membranous types was confirmed to be a 185-kDa whole molecule by immunoblotting. Correlation between the expression of c-erbB-2 protein and clinical and histological parameters was investigated. No significant correlation between 5-year survival rate of patients and expression of c-erbB-2 protein was found. In the poorly differentiated carcinoma group possessing c-erbB-2 protein, overall survival was significantly shorter than in cases without protein expression ( p < 0.01). We conclude that c-erbB-2 protein is not a useful prognostic indicator in gastric carcinomas.     

肺癌患者术前纤维支气管镜取材检测p53蛋白的诊断价值

目的研究支气管粘膜在肺癌和肺良性疾病情况下纤维支气管镜刷检涂片细胞学标本和活检组织标本中ｐ５３蛋白的表达情况,以探索在肺癌早期诊断中的价值及其与肺门或纵隔淋巴结转移的关系。方法用鼠抗人ｐ５３单克隆抗体,以ｓｐ免疫细胞组织化学方法检测ｐ５３蛋白表达。结果肺癌单纯刷检涂片及单纯活检组织中,ｐ５３蛋白表达阳性率分别为３３．３％（１２／３６）和４７．２％（１７／３６）,刷检加活检阳性率为６１．１％（２２／３６）。肺良性疾病刷检涂片及活检组织中,ｐ５３蛋白表达均为阴性,与肺癌比较,差异有显著性（Ｐ＜０．０００１）。结论术前纤维支气管镜取材检测ｐ５３蛋白可作为临床早期诊断肺癌的一个指标,ｐ５３蛋白表达与肺癌组织类型、ｐＴＮＭ分期和分化程度无关     

A monoclonal antibody to Lewis lung carcinoma variant H-59 identifies a plasma membrane protein with apparent relevance to lymph node adhesion and metastasis

Tumors H-59 and M-27, two stable metastatic variants of the Lewis lung carcinoma, differ in their ability to disseminate lymphatically. Tumor H-59 metastasizes to the regional lymph nodes regardless of the local site of growth and gives rise to widespread lymphatic dissemination, whereas tumor M-27 disseminates hematogenously without involvement of the regional nodes (P. Brodt, Cancer Res., 46: 2442-2448, 1986). In a previous paper we reported that this divergent potential to disseminate lymphatically correlated well with adhesion to frozen sections of syngeneic lymph nodes and spleens (P. Brodt, Clin. Exp. Metastasis, 7: 343-352, 1989). A monoclonal antibody (12/50) specific for tumor H-59 was subsequently generated. This antibody (an IgG1) but not three control antibodies, which reacted with tumor H-59, significantly reduced tumor cell binding to the frozen sections. Western blot analysis revealed that it recognized a plasma membrane protein of Mr 37,000 on tumor H-59 cells. No antibody binding was detected when solubilized plasma membrane preparations of tumor M-27 were used. Subsequent enzymatic assays indicated that the binding of monoclonal antibody 12/50 was insensitive to cell treatment with exoglycosidases but could be significantly reduced by pretreatment of the tumor cells with Pronase. Together these results suggest that monoclonal antibody 12/50 recognizes a cell surface adhesion protein relevant to lymphatic dissemination of this tumor.     

Expression of E-cadherin and lymph node metastasis in resected non-small-cell lung cancer

This study was conducted to clarify the relationship between E-cadherin expression on tumor and lymph node metastasis as well as its prognostic roles in resected non-small-cell lung cancer. Two hundred forty-nine patients, who underwent surgical resection (stage I-IIIA), were examined. Paraffin-embedded sections of the primary tumors in all cases and of the metastatic lymph nodes in stage IIIA disease were stained with a monoclonal antibody against E-cadherin. Decreased expression of E-cadherin correlated with pathologic stage, tumor size, lymph node metastasis, and histological grade. The 5-year survival rate of E-cadherin-negative patients with stage IIIA disease was significantly lower than that of E-cadherin-positive patients. Multivariate analysis in stage IIIA disease indicated that E-cadherin was an independent prognostic factor. In the patients with clinical N0 tumors, the frequency of pathological N2 tumors was significantly higher in cases where the primary tumor was recognized as E-cadherin expression negative than in cases where the primary tumor was recognized as positive. Decreased E-cadherin expression showed correlation with presence of lymph node metastasis in resected non-small-cell lung cancer and with the prognosis of patients with stage IIIA disease.     

Prognostic factors of secondary ovarian carcinoma

OBJECTIVE: Although the ovaries are common sites of metastases from a variety of primary neoplasms excluding carcinomas of the genital tract, there were few reports concerning survival and prognostic factors. The objective of this study was to assess the clinical factors affecting survival. METHODS: Fifty-three secondary ovarian carcinomas excluding metastases from genital tract carcinoma were registered by the Tokai Ovarian Tumor Study Group from 1989 to 1999. FIGO staging was set without considering the pathologic findings of the lymph nodes and the primary tumors. RESULTS: Twenty-four patients were stage I, 11 were stage II, 16 were stage III, and 2 were stage IV. There were significant differences in the survival curves between the early stages (I and II) and advanced stages (III and IV). The 5-year survival rate for patients without residual tumors was 39.9%, while all patients with residual tumors after surgery died within 33 months. The most frequent primary tumor was large intestinal carcinoma, and the second was gastric carcinoma. The 5-year survival rate for patients with large intestinal primary tumors was significantly better than that with stomach tumors. Multivariate analysis demonstrated that tumor stage and primary tumor sites were significant prognostic factors. CONCLUSION: FIGO staging without considering lymph node involvement and the primary tumor was a significant prognostic factor, and prognostic factors for primary ovarian carcinomas can be applied to secondary ovarian carcinomas. Furthermore, the primary tumor site was also an important prognostic factor for survival.     

HER2 overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic implications

The HER2 (c-erbB-2) receptor is overexpressed in a variety of human malignant tumors and, in breast carcinoma, has been identified as a target for anti-HER2-directed therapy with the monoclonal antibody (MAb) trastuzumab. The aim of this retrospective study was to evaluate immunohistochemic HER2 expression in a large cohort of muscle-invasive urothelial cell carcinomas of the urinary bladder and to compare the results to pathologic characteristics and survival. Paraffin-embedded tumor specimens from 138 patients undergoing radical cystectomy for muscle-invasive bladder carcinoma were studied immunohistochemically with the Food and Drug Administration (FDA)-approved HercepTest (Dako, Glostrup, Denmark). HER2 overexpression was observed in 57 of 138 tumors (41%) and occurred more frequently in high-grade carcinomas than in low-grade carcinomas (p = 0.036). No significant relationship with HER2 overexpression was registered for tumor staging and lymph node status. Kaplan-Meier curves showed a significantly worse disease-related survival (p = 0.034) in patients with HER2-overexpressing tumors compared to those without HER2 overexpression. In addition to lymph node status (p = 0.0001; relative risk [RR] = 2.93), HER2 status (p = 0.020; RR = 2.22) was identified as an independent predictor for disease-related survival in a multivariate analysis. These results suggest that HER2 expression might provide additional prognostic information in patients with muscle-invasive bladder carcinomas. Because many of these patients harbor HER2-overexpressing tumors, clinical trials evaluating the efficacy of trastuzumab in bladder carcinoma are warranted.     

Local tumor inflammation, lymph node metastasis, and survival of operated bronchus carcinoma patients

Three hundred and fifty-three resection specimens with primary lung carcinomas were cut into serial sections, and the tumor volume was computed. Resected lymph nodes were cut into 0.3-mm serial sections and analyzed for metastasis. The inflammatory reaction of lung tissue was analyzed by grading the amount of inflammatory infiltrations of a complete tumor cross section. Survival of patients was evaluated by consulting the house physician every 3 months after surgical treatment. Percentage of specimens with severe inflammatory reaction of host tissue increased remarkably in tumors with a volume of 35-60 cm3. Percentage of patients with detectable lymph node metastasis increased with tumor volume but decreased at the tumor volume of 35-45 cm3. Mean tumor volume in patients with no detectable lymph node metastasis was increased if severe inflammatory response of host tissue existed. Survival of patients with severe inflammatory infiltrations was superior to survival of patients with no inflammatory infiltrations if grouped for tumor volume. Data indicated that inflammatory infiltrations in primary lung carcinoma may partly be related to the immunologic response of host tissue to tumor growth. Inflammatory infiltrations may delay tumor cell propagation into lymph nodes or may be even able to destroy small tumor cell agglutinations.     

Skip metastasis in nonsmall cell lung carcinoma: predictive markers and isolated tumor cells in N1 lymph nodes

BACKGROUND: Skip metastasis to mediastinal lymph nodes is a prognostic factor for patients with nonsmall cell lung carcinoma (NSCLC). Little is known about the biologic behavior of tumors with noncontinuous spread to the mediastinal lymph nodes. In patients with pN2 skip metastases, micrometastases to N1 lymph nodes, which only mimic skip metastases, have not been investigated. METHODS: In a retrospective study, the authors analyzed the primary tumor specimens from 45 patients with pN2 NSCLC (18 patients had squamous cell carcinomas, 23 had adenocarcinomas, and 4 had large cell carcinomas). They immunohistochemically evaluated the expression of p21, p53, MUC-1, Bcl-2, c-ErbB-2, and E-cadherin. Survival rates and biomarker expression levels were compared between patients with pN2 disease and infiltration of N1 lymph nodes (without skip metastasis [n = 28]) and patients with pN2 disease without N1 infiltration (with skip metastasis [n = 17]). To evaluate micrometastasis in the pN1 lymph nodes of 17 patients with skip metastases, lymph nodes were stained using the anticytokeratin antibody, AE1/AE3. RESULTS: The 5-year survival rate of patients with skip metastases was 41%, compared with 14% for patients without skip metastases (P = 0.019). In a multivariate analysis, the incidence of skip metastases did not vary significantly according to gender, age, histology, pT status, or cM status. Three skip-positive patients (17.6%) had micrometastatic tumor involvement of pN1 lymph nodes. After adding these patients to the group of patients without skip metastases, there was still a significant difference in survival between the two groups. p53, MUC-1, c-ErbB-2, and E-cadherin expression levels in primary tumor specimens were not significantly different in patients with continuous metastasis and patients with skip metastases. Patients with skip metastases expressed lower levels of p21 (P = 0.026), whereas Bcl-2 expression levels were considerably higher (P = 0.019) compared with the corresponding levels in patients without skip metastases. CONCLUSIONS: Patients with NSCLC and pN2 skip metastases have a more favorable prognosis than do patients with pN2 disease without skip metastases. Tumor specimens from these patients exhibit elevated expression of the antiapoptosis gene BCL2 and lower expression levels of p21 relative to patients with pN2 disease without skip metastases. Micrometastases occurred in 3 of 17 (17.6%) patients with pN2 disease and skip metastases diagnosed by routine histopathology.     

The expression of monoclonal antibody KM-93 reactive antigen in human lung carcinoma--an immunohistochemical evaluation

Using an histochemical technique, the expression of a tumor-associated antigen, recognized by the monoclonal antibody KM-93, has been investigated in 39 cases of human lung cancer. The overall positive rate was found to be 87.2%, this breaking down to 90.9%, 80.0%, and in adenocarcinomas, squamous cell carcinomas, and large cell carcinomas, respectively. In adenocarcinomas, most of the tumor cells stained strongly, while in squamous cell carcinomas, differentiated cells tend to react with the antibody. Even, in tumors judged to be negative, a small fraction of stained cells also was noted. These results suggest the clinical usefulness of this antibody.     

A monoclonal antibody (B72.3) defines patterns of distribution of a novel tumor-associated antigen in human mammary carcinoma cell populations

We report here both the range and patterns of reactivity of an IgG1 monoclonal antibody, B72.3, prepared against human, metastatic mammary carcinoma cells. When the avidin-biotin complex (ABC) immunoperoxidase technique was used on tissue sections, monoclonal B72.3 reacted with 19 of 41 (46%) primary mammary carcinomas and 13 of 21 (62%) metastatic lesions, either in axillary lymph nodes or at distal sites. Variable concentrations of antigen, recognized by B72.3, were observed among mammary tumors, as well as among different cell populations of a given tumor mass. Several patterns of antigen distribution were observed: membrane, diffuse cytoplasmic, focal and marginal. No reactivity was observed to normal mammary epithelium, stroma, or lymphocytes of the breast, nor to any cell types in a variety of other normal human tissues, melanomas, and sarcomas. Reactivity with all of four colon carcinomas was also observed. Assay of serial sections of mammary carcinomas with B72.3 and a monoclonal antibody directed against carcinoembryonic antigen demonstrated that these antigens were both distinct and non-coordinately expressed.     

Evaluation of p53 alterations in occult lymph node metastases

BACKGROUND AND OBJECTIVES: This study was designed to evaluate p53 alterations in occult lymph node metastases. METHODS: We examined 41 patients with stage I non-small-cell lung cancer. We investigated p53 gene mutation by polymerase chain reaction and single-strand conformation polymorphism analysis of exons 5-8, p53 protein accumulation by immunostaining with monoclonal antibody DO-7, and detection of tumor cells in lymph nodes by immunohistochemistry with monoclonal antibodies to cytokeratin (CK). RESULTS: p53 gene mutation was detected in 34% of tumors and nuclear p53 accumulation in 46%. CK-positive cells in the hilar and mediastinal region lymph nodes were detected in 43.9% of patients and 29.3%, respectively. Of the 14 cases with p53 mutation and the 19 cases with p53 accumulation, 12 and 15 had micrometastases in the hilar or mediastinal lymph nodes, respectively. However, p53 alterations were not significantly associated with occult lymph node metastases. In cases with occult lymph node metastases, the 5-year survival was 81. 9% for the p53 wild-type group and 45.8% for the p53 mutation group. CONCLUSIONS: p53 alterations are not correlated with occult lymph node metastases, while p53 gene mutation is considered to be an unfavorable prognostic marker in patients with occult lymph node metastases. J. Surg. Oncol. 2000;73:143-147.     

Dukes′B期大肠癌微小转移及P53检测的临床意义

目的　Dukes′B期大肠癌患者手术后 5年生存率为 5 3.9%～ 84.9% ,有部分患者 5年内出现局部复发或 /和远处转移。本研究旨在探讨淋巴结微小转移灶 (lymphnodesmicrometastasisLMM)及原发灶p5 3的表达对评估经手术切除原发肿瘤及肠周淋巴结的Dukes′B期大肠癌患者预后的重要性和指导术后治疗的意义。方法　收集 5 2例Dukes′B期大肠癌患者手术切除的淋巴结及原发灶石蜡标本 ,同时获得这些病例的临床资料及随访 (生存期大于五年或死亡 )资料 ;实验方法 ;以细胞角蛋白单抗 (anti cytokerratinAE1/AE3 )为探针 ,采用免疫组化SAP(streptavidin alkalinephosphatase)法检测淋巴结中的LMM。以p5 3单抗为探针 ,采用免疫组化S -P(streptavidin peroxidase)法检测原发灶p5 3蛋白的表达。结果　检测 5 2例Dukes′B期大肠癌患者的 5年生存率为 73% ( 38/5 2 )。淋巴结中LMM +组 5年生存率 45 .5 % ( 5 /11) ,LMM 组 78.9% ( 32 /41)。原发灶中p5 3+组 5年生存率 6 2 % ( 18/2 9) ,p5 3 组 87% ( 2 0 /2 3)。同时检测LMM +p5 3+组 33% ,LMM p5 3 组 84%。X2 检验均P <0 .0 5 ,生存分析log rank检验P <0 .0 5。本实验中一般因素 (性别、年龄及肿瘤所在部位 )对检测结果的影响不明显 ;统计学处理 ,P >0 .0 5。结论　用     

Characterization of a human monoclonal antibody with broad reactivity to malignant tumor cells

Lymphocytes from mediastinal lymph nodes of 9 patients with primary lung cancer were fused with murine myeloma cells (P3U1). One of the clones (4G12) was stable for secretion (10 micrograms/ml) of human IgM lambda for 24 months. The antigen detected by 4G12 was sensitive to both trypsin and periodic acid-Schiff treatment. It immunoprecipitated a glycoprotein with an Mr of 65,000 upon analysis in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reduced conditions. Immunohistochemical staining demonstrated that 4G12 possessed a high reactivity to squamous cell carcinomas of the lung (29 of 29) and also reacted with other lung carcinomas [adenocarcinomas (14 of 20) and large cell carcinomas (3 of 8)] and with some nonpulmonary malignant tumors (15 of 56). However, it did not react with small cell carcinomas of the lung. No benign tumors (0 of 26) so far tested have been positive. 4G12 did not react with most of the normal tissues; an exception was that it was weakly reactive on the glandular cells of the trachea and bronchi and on the proximal tubular cells of the kidneys. Thus 4G12 showed a broad reactivity to malignant tumors (68% of lung carcinomas, 27% of nonpulmonary carcinomas, and 0% of benign tumors). The reactivity of 4G12 on tissues from squamous cell carcinomas of the lung indicated that the expression of the antigenic determinant was much more in the well-differentiated grade than in the poorly differentiated grade. Thus the antigen detected by 4G12 appears to be related to tumor differentiation. Moreover, fluorescence-activated cell sorter analysis demonstrated that the expression of the antigen epitope depended on the cell cycle (G2-M). These data suggest that the 4G12 monoclonal antibody detects a new tumor-associated antigen that is recognized by the human immune system.     

PN0胃癌淋巴结微转移的检测及其预后意义

目的　评估细胞角蛋白免疫组化染色诊断PN0 胃癌区域淋巴结微转移的临床病理意义。方法　采用免疫组织化学方法 ,用细胞角蛋白 19单抗检测了 3 9例经传统HE染色诊断为无转移 (PN0 )胃癌患者的 3 74个淋巴结。结果　淋巴结微转移率为 3 3 .3 % ( 13 /3 9) ,微转移度为 4.5 % ( 17/3 74) ,微转移与其它临床病理特点无显著相关性 (P >0 .0 5 )。微转移阳性者与阴性者总生存率显著不一致 (P =0 .0 2 73 )。多变量分析表明淋巴结微转移是独立的预后因素。结论　细胞角蛋白 19单抗免疫组化染色方法较常规组织学检查方法敏感性更高 ,提高了淋巴结微转移的检出率和临床分期的准确性。淋巴结微转移对胃癌预后有重要作用