The prognostic significance of the increase in the serum M30 and M65 values after chemotherapy and relationship between these values and clinicopathological factors in patients with advanced gastric cancer

In some studies, the prognostic and predictive significance of M30 and M65 has been reported to detect response to chemotherapy. In the present study, we aimed at determining the changes of serum M30 and M65 values after chemotherapy and the impact of these values on treatment response and progression-free survival (PFS) and overall survival (OS) of patients with advanced gastric cancer. A total of 31 patients with advanced gastric cancer was included. M30 and M65 values were measured by a quantitative enzyme-linked immunosorbent assay (ELISA) method in serum samples before and 48?h after the first chemotherapy cycle. Pre- and postchemotherapy values of M30 and M65 were compared. The difference between the mean values of serum M30 and M65 before and after chemotherapy was calculated and the prognostic significance of changes for survival was evaluated by univariate and multivariate analysis. Logistic regression analysis was performed to predict response to chemotherapy. Serum M30 and M65 levels were found to be increased significantly after chemotherapy (M30, 582.7?±?111.5 U/l [pre mean] vs. 983.3?±?214.1 U/l [post mean], p?=?0.01; M65, 2,061.7?±?431.2 U/l [pre mean] vs. 2,646.3?±?433.1 U/l [post mean], p?=?0.003). Means of the differences of M30 and M65 levels before and 48?h after chemotherapy were 400.5?±?190 U/l ([M30-difference] M30-D) and 584.6?±?335.4 U/l (M65-D), respectively. Patients with serum M30-D of <400.5 U/l had better median PFS and OS times than patients with M30-D >400.5 U/l (PFS, 9.9 vs. 4.3?months, p?=?0.018 and OS, 13.6 vs. 8.1?months, p?=?0.029). In addition, median PFS and OS intervals in patients with serum M65-D?>?584.6 U/l were significantly worse than those of patients whose M65-D was lower than or equal to 584.6 U/l (4.1 vs. 11.4?months for PFS, p?=?0.002 and 5.7 vs. 13.6?months for OS, p?=?0.005). Patients with values above M30-D and M65-D had a better tumor response compared with patients with values below M30-D and M65-D (p?=?0.02 and p?=?0.006, respectively). In the logistic regression analysis, only M65-D was significantly found to be an independent factor in predicting response to chemotherapy (p?=?0.018, OR:1.4). However, only M30 levels after chemotherapy were found to be an independent prognostic factor for PFS in the multivariate analysis. These results showed for the first time that both M30 and M65 in serum samples of patients with advanced gastric cancer were elevated 48?h after chemotherapy and these were poor prognostic factors for both PFS and OS of patients. Moreover, increased serum M65 levels after chemotherapy can be predict tumor response.     

A follow-up report on a new method of segmental resection for small-sized early lung cancer

We previously reported a new method of segmentectomy, pulmonary artery-guided segmentectomy as a surgical alternative for small-sized early lung cancer with favorable results, but the follow-up time was too short for definitive conclusion. To examine the efficacy of the segmentectomy, and to determine the appropriate surgical procedure for early lung cancer, we conducted a retrospective follow-up study, and examined the influences of tumor size and preoperative serum tumor marker levels on the prognosis. We reviewed the records of 91 patients who underwent the segmentectomy for pathological T1N0M0 non-small cell lung cancer from 1993 to 2002. In 85 patients, carcinoembryonic antigen, squamous cell carcinoma-related antigen, and a fragment of cytokeratin were measured preoperatively. The overall 5-year survival rate was 83%. Indication (intentional, n=47; compromised, n=44) and tumor size (20mm or less, n=68; 21 to 30 mm, n=23) had no significant impact on survival. The 5-year survival rate for 49 patients with normal tumor marker levels was 93%, and significantly higher than 36 patients with at least one elevated tumor marker level (68%, p<0.01). Median follow-up time of 72.0 months revealed 11 locoregional recurrences. The incidence of locoregional recurrence was significantly higher in the patients with tumors of 21-30 mm, and elevated tumor marker (p<0.01). The follow-up study demonstrated that the segmentectomy could be an acceptable surgical treatment for early lung cancer patients with tumors of 20mm or smaller and normal tumor marker levels.     

The roles of chemotherapy and surgery in gastric carcinoma and the influence of prognostic factors on survival

In this study, we present the results of surgery and chemotherapy and the impact of various prognostic factors on survival in patients with gastric carcinoma with a follow-up of 6 years. All of the 328 cases were adenocarcinoma histologically and had a median age of 55 years. Median survival was 11 months, and the 5-year survival rate was 18%. Nonmetastatic cases were associated with improved survival as compared with the cases with metastatic disease (p<0.001). Patients with gastrectomy had improved survival (p<0.001). Subtotal gastrectomized patients had better survival rates in comparison to the total gastrectomized patients (p = 0.03). Addition of splenectomy to total gastrectomy and adjuvant chemotherapy did not influence survival rates (p>0.05). In metastatic patients, we determined beneficial effects of gastrectomy and chemotherapy on survival. The benefit was most predominant in chemoresponsive patients (p<0.001). Higher serum CA 19.9 levels in patients without metastases, higher serum lactate dehydrogenase and carcinoembryonic antigen levels in patients with metastases, and lower serum albumin levels in both stages were determined as significant predictors of poor survival. On multivariate analysis, only higher serum CA 19.9 level was the independent unfavorable prognostic factor of survival time in nonmetastatic patients (p = 0.008). In metastatic disease, older age (p = 0.03) and male gender (p = 0.05) were associated with poorer survival. In conclusion, gastric cancer is a great health problem, especially in developing countries, and we need more optimal approaches and treatment modalities for gastric cancer.     

Serum M65 as a Biomarker for Metastatic Renal Cell Carcinoma

Introduction/BackgroundEffective cancer biomarkers for early detection, prognosis, or therapy response prediction are urgently need in metastatic RCC. M30 and M65 are released during apoptotic cell death and precisely reflect epithelial tumor cell death. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in predicting survival rates for patients with metastatic RCC.Patients and MethodsThirty-nine patients with metastatic RCC and 39 healthy control subjects were included in this study. Serum M30 and M65 levels were measured by ELISA.ResultsThe median ages of the patients and control subjects were 60 and 58 years, respectively. No difference was detected in the median serum M30 level between the patients and control subjects (53.7 vs. 49.1 U/L; P = .31). The median serum M65 level was significantly higher in patients than in control subjects (334.0 vs. 179.1 U/L; P < .001). Receiver operating characteristic analysis revealed that the best cutoff value for serum M65 level for predicting progression-free survival (PFS) was 313.6 U/L. The median PFS of patients whose M65 levels were ≤ 313.6 U/L was better than that of patients whose M65 levels were > 313.6 U/L (P = .03).ConclusionTo the best of our knowledge, this is the first study to evaluate serum M30 and M65 levels in patients with RCC. Serum M65 levels were significantly elevated in patients with metastatic RCC compared with healthy individuals. In addition, the serum M65 level could be predictive of PFS in patients with RCC.     

The value of serum Bcl-2 levels in advanced lung cancer patients

Overexpression of the Bcl-2 protein was associated with a favorable prognostic factor for survival in lung cancer patients, especially nonsmall cell lung carcinoma. The present study was conducted to investigate the value of serum Bcl-2 levels in advanced lung cancer patients. Fifty patients with advanced lung carcinoma pathologically verified and 18 healthy controls were investigated. Serum samples were obtained on the first admission before the chemotherapeutic treatment were given. Serum Bcl-2 levels were determined by using anti-Bcl-2 monoclonal coating antibody. The baseline serum Bcl-2 levels were significantly higher in patients with lung cancer than in the control group (p<0.001). Serum Bcl-2 levels were elevated in 48 (96%) advanced lung cancer patients. None of the prognostic parameters analyzed, such as age of patient, gender, histology, stage of disease, erythrocyte sedimentation rate, serum albumin, hemoglobin, CEA, NSE, LDH, performance of patient, weight loss, and response to chemotherapy, was significantly correlated with Bcl-2 serum concentrations. The serum Bcl-2 concentrations were not changed with cisplatin-based cytotoxic chemotherapy regardless of response (p=0.76). No prognostic value of serum Bcl-2 was determined. In conclusion, the results of the present study, which is the first study to determine serum Bcl-2 levels in lung cancer, suggest that decreased apoptosis occurred due to the effect of serum Bcl-2 elevation in lung cancer patients. Serum Bcl-2 level was of diagnostic but not prognostic value in lung cancer patients. However, more studies are needed to define the role of Bcl-2 in the diagnosis and prognosis of lung cancer.     

Response to neoadjuvant chemotherapy in breast cancer could be predictable by measuring a novel serum apoptosis product, caspase-cleaved cytokeratin 18: a prospective pilot study

The M30-monoclonal antibody recognizes a neo-epitope of cytokeratin 18 which is formed after caspase-cleavage during apoptosis. Caspase-cleaved cytokeratin 18 is released from apoptotic cells into circulation. The aim of this study was to evaluate the relationship between M30-antigen level and chemotherapy response in neoadjuvant treatment of breast cancer. Forty-two patients with invasive breast carcinoma received 4 cycles of anthracycline based neoadjuvant chemotherapy. Serum samples were obtained for assessment of M30-antigen levels before the administration of first chemotherapy cycle (baseline), and then after 24 and 48 hours for determination of chemotherapy induced apoptosis. M30-antigen levels at 24 and 48 hours were found to be significantly higher than baseline (p < 0.001, p = 0.003, respectively). M30-antigen levels in responders showed statistically significant increases at 24 and 48 hours (p < 0.001; p = 0.004, respectively), while statistically significant increases were not observed in nonresponders. Percentage change of M30-antigen levels was significantly higher in responders than nonresponders at 24 hours (p = 0.020). In conclusion, our study revealed a significant relationship between increases of M30-antigen levels in serum and overall response to therapy.     

M30/M65 ratio predicts the outcome of paclitaxel chemotherapy for NSCLC

Purpose

Paclitaxel is an effective treatment for some of the non-small-cell lung cancer (NSCLC) patients. However, prediction of the outcome of paclitaxel treatment at the early stage of the chemotherapy is difficult. M30 and M65 are circulating fragments of cytokeratin 18 released during apoptosis or necrosis, respectively, and have been used as markers to evaluate chemotherapy in some cancers. Here, we aimed to examine M30 and M65 values for predicting the therapeutic outcome of paclitaxel treatment of NSCLC.

Methods

The serum levels of M30 and M65 before and after paclitaxel treatment in advance-stage NSCLC patients were analyzed, and compared to those in healthy controls. The importance of the M30 and M65 levels to the outcome of chemotherapy was analyzed.

Result

We found that the serum M30 and M65 levels were higher in patients with NSCLC (n = 44) than in control healthy subjects (n = 56) (p < 0.001). Two days after paclitaxel treatment, the serum levels of both M30 and M65 significantly increased in NSCLC patients (p < 0.001). Neither marker alone significantly correlated with overall patient survival, but the ratio of M30 vs M65 appeared to be an important prognostic factor for the overall survival of the patients (p < 0.01).

Conclusion

Our results suggest that the serum M30/M65 ratio may be a prognostic factor for the outcome of paclitaxel treatment in NSCLC.

     

A close association between alteration in growth kinetics by neoadjuvant chemotherapy and survival outcome in primary breast cancer

Few surrogate markers are available for predicting the survival benefit from chemotherapy in primary breast cancer. We examined tumor growth kinetics by assessing cytokeratin 18 neo-epitope (CK18NE), an apoptosis marker detected by M30 antibody and Ki-67 antigen, a proliferation marker detected by MIB-1 antibody in 72 primary breast cancer patients who underwent pre-operative anthracycline-based chemotherapy. Increase in M30 index and decrease in MIB-1 index after the exposure of 2 to 4 cycles of chemotherapy correlated significantly with pathological tumor response. Univariate survival analysis, conducted in the subgroup of 42 patients who underwent CAF (cyclophosphamide, adriamycin and 5-FU) therapy alone, showed that the patients with the high levels of M30 index (>35 counts/1000 tumor cells) and the low levels of MIB-1 index (<140 counts/1000 tumor cells) after chemotherapy had a remarkably favorable prognosis as compared with patients in other categories. In addition, the alteration in growth kinetics by the treatment showed a significant prognostic value. Multivariate analysis also confirmed that the post-treatment growth kinetics was an independent prognostic indicator. These findings suggest that the alteration in growth kinetics revealed by CK18NE and MIB-1 might be a surrogate marker for predicting the survival benefit from chemotherapy in primary breast cancer.     

胸腔镜联合化疗与单纯化疗对晚期非小细胞肺癌患者预后的影响

目的 评价胸腔镜联合化疗与单纯化疗对晚期非小细胞肺癌患者治疗后肺功能、生存率和生活质量的影响.方法 选取晚期非小细胞肺癌患者125例,依据随机原则并结合患者选择意愿将患者分为2组:胸腔镜联合化疗组(n=65),单纯化疗组(n=60).计算随访时患者生存时间或患者死亡时间,并计算3年随访期间的死亡率.患者整个治疗结束后4周行肺功能检测.随访患者KPS评分,取其生存期限内的KPS评分的平均值.结果 随访患者治疗后的中位生存期和生存率,胸腔镜联合化疗组患者优于单纯化疗组的患者,差异有统计学意义(P＜0.05).胸腔镜联合化疗组的肺功能指标均优于单纯化疗组的患者,差异有统计学意义(P＜0.05).患者治疗后KPS评分在55～85分之间,胸腔镜联合化疗组患者优于单纯化疗组的患者,差异有统计学意义(P＜0.05).结论 非小细胞肺癌患者行胸腔镜联合化疗后,其肺功能、生存率和生活质量优于单纯化疗后的患者.     

Anti-Heat Shock Protein-27 Antibody Levels in Women with Breast Cancer: Association with Disease Complications and Two-Year Disease-Free Survival

Background and Aim: Breast cancer is a major healthcare problem in women. There are many reports about up-regulation of Hsp27 in cancer tissues but less is known about the potential relationship between Hsp27 antibody levels and breast cancer complications. We here investigated concentrations of serum Hsp27 antigen and antibodies in subjects with and without breast cancer and assessed potential associations with two-year disease-free survival, histological grade and number of lymph nodes. Materials and Methods: Specifically, serum Hsp27 antigen and antibody levels from 97 patients with breast cancer, and 65 healthy controls were determined by enzyme-linkedimmunosorbent assays (ELISAs). Results: Serum Hsp27 and antibody levels were significantly (p<0.001) higher in patients with breast cancer compared to the control group, but no relationship were found with two-year disease free survival, histological grade or number of lymph nodes (p> 0.6, 0.2 and 0.9 respectively). Conclusions: Elevated levels of Hsp27 antibody occur in patients with women with breast cancer but do not appear to be associated with the presence of disease clinical complications.     

多项肺系统肿瘤标志物异常在晚期肺腺癌治疗中的作用

背景与目的 肺癌的常用肿瘤标志物中,癌胚抗原(carcinoembryonic antigen, CEA)与糖类抗原125(carbohydrate antigen 125, CA125)、细胞角蛋白19片段(cytokeratin 19, CYFRA21-1)与鳞状细胞癌抗原(squamous carcinoma antigen, SCC)、神经元特异性烯醇化酶(neuron specific enolase, NSE)与胃泌素释放肽前体(pro-gastrin-releasing peptide, ProGRP)分别在肺腺癌、肺鳞状细胞癌和小细胞肺癌中有较高表达.本研究旨在通过对比多项肿瘤标志物异常(A组)和仅CEA和/或CA125异常(B组)的两组晚期肺腺癌患者,探讨多项肿瘤标志物异常在疗效评价和预测复发方面的价值.方法 纳入中国医学科学院肿瘤医院的IV期肺腺癌初治病例,回顾性分析其临床数据,包括临床特征、治疗前的血清肿瘤标志物水平、疗效及无进展生存期.结果 除CEA和CA125外,A组异常比率最高的肿瘤标志物是CYFRA21-1(93%),其次是NSE(36%)、SCC(13%)和ProGRP (12%).多项肿瘤标志物异常的患者更易出现远处多部位转移(P<0.001),治疗后的无进展生存期更短(中位时间5.3个月 vs 7.3个月,P=0.016).两组中进行维持治疗的患者均比未行维持治疗的患者复发风险低(P均<0.001).结论 多项肿瘤标志物异常患者复发风险高,维持治疗可降低复发风险.     

Preoperative serum tissue polypeptide‐specific antigen is a valuable prognostic marker in breast cancer

Tissue polypeptide‐specific antigen (TPS), a specific epitope structure of a peptide in serum associated with human cytokeratin 18, is linked to the proliferative activity of tumors. Here, we aimed to identify the association between the preoperative serum TPS level and outcome in breast cancer patients. We assayed preoperative serum TPS levels in 1,477 breast cancer patients treated between June 2000 and December 2006. The TPS level was measured with a one‐step solid phase radiometric sandwich assay detecting the M3 epitope on cytokeratin 18 fragments. The cutoff value was 80 U/L. Among the 1,477 breast cancer patients examined, preoperative serum TPS level was elevated (>80 U/L) in 290 patients (19.6%). Age (>45 years), tumor size (>2 cm), nodal metastasis, negative progesterone receptor and human epidermal growth factor receptor 2 were associated with elevated TPS. Evidence of recurrence was observed in 229 patients (15.6%). Elevated TPS was associated with poor disease‐free survival (p < 0.001) and overall survival (p < 0.001). In a multivariate analysis using the Cox proportional regression model, elevated TPS was an independent prognostic factor for disease‐free survival (p = 0.001) and overall survival (p = 0.026). Furthermore, in subgroup analysis based on molecular subtype, the prognostic effect of preoperative TPS on survival (OS: HR 2.614, p = 0.003; DFS: HR 1.895, p = 0.001) was identified only in the luminal A subtype. Elevated preoperative serum TPS level is associated with poor breast cancer outcomes. Based on these findings, we conclude that preoperative TPS is a valuable biomarker for clinical use in predicting outcomes in breast cancer patients.     

An evaluation of the impact of a multidisciplinary team, in a single centre, on treatment and survival in patients with inoperable non-small-cell lung cancer

Treatment and survival of patients with inoperable Non-small-cell lung cancer in 1997 (n=117) and 2001 (n=126), before and after the introduction of a multidisciplinary team, was examined in a single centre. There were no differences in age, sex and extent of deprivation between the two years. However, in 2001, 23% of patients received chemotherapy treatment compared with 7% in 1997 (P<0.001). Median survival in 2001 was 6.6 months compared with 3.2 months in 1997 (P<0.001).     

Role of thoracic radiotherapy combined with chemotherapy in limited stage small cell lung cancer (SCLC). A randomized multicenter phase III trial

We initiated a prospective randomized multicenter trial to clarify the role of radiotherapy in the treatment of the primary tumor in small cell lung cancer stage limited disease. Patients were randomized to receive only chemotherapy (n = 27), or chemotherapy and radiotherapy of 30 Gy (n = 34) or chemotherapy and radiotherapy of 50 Gy (n = 30). Radiotherapy was administered after the third chemotherapy cycle. All patients received prophylactic total-brain irradiation of 30 Gy. The chemotherapy consisted of 6 cycles of adriamycin, cyclophosphamide and vincristin (ACO). 415 patients entered the trial. According to eligibility criteria 97 patients were randomized and 91 patients were evaluable for response. The total response rate (CR and PR) was 69% not being statistically different between all groups. No differences in survival time were observed between patients receiving 30 Gy (median = 13.5 months) and those receiving 50 Gy (median = 12.4 months). However patients treated with radiotherapy and chemotherapy showed a statistically significant improvement of survival time compared to patients receiving chemotherapy alone (median = 9.7 months).     

实时监测癌细胞死亡早期预测化疗疗效的研究

目的:探讨实时监测癌细胞死亡早期血清中CK18含量预测化疗疗效的可行性。方法:癌细胞死亡后释放的可溶性细胞内大分子可于血清中检出；CK18是上皮细胞的细胞骨架蛋白，CK18-Asp396是CK18在癌细胞凋亡过程中的产物，可被M30抗体特异性检出，M65抗体可检出CK18在癌细胞死亡过程中产生的所有可溶性片段。CK18-Asp396和可溶性CK18总量的变化可用于监测癌细胞的凋亡和死亡。本实验在30例乳腺癌患者中检测化疗前和第1 周期化疗给药结束后24～48h 血清中CK18-Asp396和可溶性CK18总量；采用卡方检验分析第1 周期化疗前后CK18-Asp396和可溶性CK18总量变化率与4 周期后化疗疗效之间的关系。结果:30例乳腺癌患者中，ⅡB 期2 例，ⅢA 期11例，ⅢB 期1 例，ⅢC 期2 例，Ⅳ期14例，均接受以蒽环类和/或紫杉类为基础的联合化疗，4 周期后按RECIST标准进行疗效评价，共有3 例完全缓解，19例部分缓解，7 例稳定，1 例进展，有效率为73.3%（22/30）。 化疗前和第1 周期给药结束24～48h 血清CK18-Asp396变化率>20% 和/或CK18总量变化率>30% 的19例患者均为缓解，而其余的11例患者中仅3 例部分缓解，7 例稳定，1 例进展（χ2=18.843，P=0.001）。 结论:乳腺癌患者化疗前和第1 周期给药结束24～48h 血清中不同片段CK18含量的变化率与化疗疗效明显相关，作为预测乳腺癌及其它上皮来源恶性肿瘤化疗疗效的生物学指标具有进一步研究的价值。      

Efficacy of First-line Chemotherapy Affects the Second-Line Setting Response in Patients with Advanced Non-Small Cell Lung Cancer

Background: Chemotherapy is the mainstay of treatment for the majority of patients with advanced nonsmall cell lung cancer (NSCLC) without driver mutations and many receive therapies beyond first-line. Secondline chemotherapy has been disappointing both in terms of response rate and survival and we know relatively little about the prognostic factors. Materials and Methods: One thousand and eight patients with advanced NSCLC who received second-line chemotherapy after progression were reviewed in Shanghai PulmonaryHospital, China, from September 2005 to July 2010. We analyzed the effects of potential prognostic factors on the outcomes of second-line chemotherapy (overall response rate, ORR; progression free survival, PFS; overall survival, OS). Results: The response and progression free survival of first-line chemotherapy affects the ORR, PFS and OS of second-line chemotherapy (ORR: CR/PR 15.4%, SD 10.1%, PD2.3%, p<0.001; PFS: CR/PR 3.80 months, SD 2.77 months, PD 2.03 months, p<0.001; OS: CR/PR 11.60 months, SD 10.33 months, PD 6.57 months, p=0.578, p<0.001, p<0.001, respectively). On multivariate analysis, better response to first-line therapy (CR/PR: HR=0.751, p=0.002; SD: HR=0.781, p=0.021) and progression within 3-6 months (HR=0.626, p<0.001), together with adenocarcinoma (HR=0.815, p=0.017), without liver metastasis (HR=0.541, p=0.001), never-smoker(HR=0.772, p=0.001), and ECOG PS 0-1 (HR=0.745, p=0.021) were predictors for good OS following secondline chemotherapy. Conclusions: Patients who responded to first-line chemotherapy had a better outcome after second-line therapy for advanced NSCLC, and the efficacy of first-line chemotherapy, period of progression, histology, liver metastasis, smoking status and ECOG PS were independent prognostic factors for OS.     

化疗联合DC-CTL治疗不同分期非小细胞肺癌的疗效分析

目的:分析化疗联合树突状细胞诱导的细胞毒性T淋巴细胞(dendritic cells and cytotoxic lymphocytes,DC-CTL)对非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的疗效及安全性.方法:收集我院2013年5月至2015年12月期间住院病理确诊为Ⅰb(具有高危因素)、Ⅱa、Ⅱb、Ⅲa、Ⅲb、Ⅳ期的NSCLC患者114例,其中接受肺癌根治术的患者分为术后化疗联合DC-CTL组20例和术后化疗组32例,未行手术患者分为化疗联合DC-CTL组23例和化疗组39例.回顾分析了114例患者的临床特点、疾病控制率(disease control rate, DCR)、中位无疾病生存期(median-disease free survival,M-DFS)、中位无进展生存期(median-progression free survival,M-PFS)、副作用等资料.随访截止至2016年11月.结果:1年DCR:术后化疗联合DC-CTL组(75.0%)vs术后化疗组(43.8%)(P=0.044).M-DFS:术后化疗联合DC-CTL组(19.5个月)与术后化疗组(11.5个月)相比,差异具有明显统计学意义(P=0.025 5).化疗联合DC-CTL治疗与化疗组相比,DCR及M-PFS不具有统计学差异.DC-CTL治疗的副作用显著低于化疗.结论:术后化疗联合DC-CTL治疗可显著提高DCR及延缓NSCLC患者的疾病进展,且安全性高.     

Comparison of breast cancer mucin (BCM) and CA 15-3 in human breast cancer

Summary The Breast Cancer Mucin (BCM) enzyme immunoassay utilizes two monoclonal antibodies (Mab), M85/34 and F36/22, for the identification of a mucin-like glycoprotein in serum of breast cancer patients. We have compared BCM with CA 15-3, another member of the human mammary epithelial antigen family.Serum BCM was evaluated in 151 and CA 15-3 in 134 patients with breast cancer, in 30 normal controls, in 9 pregnant women, and in 13 cancer patients (non-breast). Neither the normal controls nor the pregnant women had BCM levels > 25 U/ml. In contrast, 87 of 115 patients (75%) with metastatic breast cancer had BCM levels > 25 U/ml. All control persons had CA 15-3 levels < 25 U/ml, but 2 out of 9 pregnant women (22%) had levels > 25 U/ml. Seventy-four out of 97 patients (76%) with metastatic breast cancer had CA 15-3 levels > 25 U/ml.A statistically significant correlation was found between BCM and CA 15-3 in the breast cancer patient group (r = 0.883, p < 0.001, n = 134) and in the normal control group (r = 0.743, p < 0.001, n = 30). BCM and CA 15.3 both showed no correlation with CEA in breast cancer patients (r = 0.060, n = 81; and r = 0.146, n = 78, respectively). BCM had a range of sensitivity similar to that of the CA 15-3 RIA.Our results suggest that BCM may be a useful new marker for monitoring the clinical course of patients with breast cancer. Furthermore, in the evaluation of breast cancer patients, marker pands depending on disease stage may be a better choice than any single parameter in the evaluation of breast cancer patients.     

Epidermal growth factor receptors in cancer tissues of esophagus, lung, pancreas, colorectum, breast and stomach

The levels of epidermal growth factor (EGF) receptors were investigated in surgically resected tumors of various origins including esophagus (n = 33), lung (n = 14), pancreas (n = 9), colorectum (n = 10), breast (n = 23) and stomach (n = 8). The 125I-EGF binding capacities of squamous cell carcinomas of esophagus and lung were exceptionally higher than those of the other cancer tissues. Immunohistochemical staining with an anti-EGF receptor monoclonal antibody detected EGF receptors in the basal cells and parabasal cells of normal esophageal epithelium and in all the cancer cells of squamous cell carcinoma tissues of esophagus and lung. DNA replicating cells were examined by the bromodeoxyuridine staining method and it was found that the basal cells and parabasal cells of normal epithelium and peripheral cells of cancer pearls are proliferating. Contrary to this, a tumor antigen TA-4, known as a specific marker for squamous carcinoma, was detected in the differentiated cancer cells and in middle-layer squamous cells. These results strongly suggest that the increase in EGF receptor levels may be associated with the development of human squamous cell cancers of esophagus and lung. Thus, measurement of EGF receptor expression in tumor tissues has diagnostic value and should prove useful for the development of new therapies.     

Epidermal Growth Factor Receptors in Cancer Tissues of Esophagus, Lung, Pancreas, Colorectum, Breast and Stomach

The levels of epidermal growth factor (EGF) receptors were investigated in surgically resected tumors of various origins including esophagus (n = 33), lung (n = 14), pancreas (n = 9), colorectum (n = 10), breast (n = 23) and stomach (n = 8). The ¹²⁵I-EGF binding capacities of squamous cell carcinomas of esophagus and lung were exceptionally higher than those of the other cancer tissues. Immunohistochemical staining with an anti-EGF receptor monoclonal antibody detected EGF receptors in the basal cells and parabasal cells of normal esophageal epithelium and in all the cancer cells of squamous cell carcinoma tissues of esophagus and lung. DNA replicating cells were examined by the bromodeoxyuridine staining method and it was found that the basal cells and parabasal cells of normal epithelium and peripheral cells of cancer pearls are proliferating. Contrary to this, a tumor antigen TA-4, known as a specific marker for squamous carcinoma, was detected in the differentiated cancer cells and in middle-layer squamous cells. These results strongly suggest that the increase in EGF receptor levels may be associated with the development of human squamous cell cancers of esophagus and lung. Thus, measurement of EGF receptor expression in tumor tissues has diagnostic value and should prove useful for the development of new therapies.