Immunohistochemical staining of bone marrow biopsies for detection of occult metastasis in breast cancer

Summary Immunohistochemical (IHC) techniques should allow for a greater detection of bone marrow micrometastasis in patients with breast carcinoma. We studied a series of bone marrow (BM) biopsies negative by conventional histologic techniques from 93 patients with breast carcinoma. Prior to this study, twelve BM biopsies, positive by conventional histology, were stained with a panel of monoclonal antibodies (MoAb), directed either against cytokeratin (KL1, AE1-AE3, CAM5-2) or epithelial membrane antigen (EMA, HMFG2). KL1 appeared to be the most sensitive of the markers used in the detection of metastases and is available commercially. It therefore was the only MoAb used with the series of 93 BM biopsies negative by conventional examination. Within this series, among 45 patients clinically suspected of having bone marrow metastasis but with BM biopsies negative by conventional staining, one case showing myelofibrosis stained positive with KL1 demonstrating isolated tumor cells. For the 48 patients without suspicion of bone marrow metastasis at initial diagnosis for breast carcinoma, KL1 revealed no marrow metastasis.Single bone marrow biopsy techniques whether stained by conventional or IHC methods do not appear to be useful tests to detect occult bone marrow metastasis, especially at initial diagnosis of clinically M_o breast carcinoma patients.     

Prognostic significance of micrometastatic bone marrow involvement

The present review focuses on the methodology and clinical significance of new diagnostic approaches to identify micrometastatic breast cancer cells present in bone marrow (BM), as a frequent site of overt metastases. Using monoclonal antibodies (mAbs) to epithelial cytokeratins (CK) or tumor-associated cell membrane glycoproteins, individual carcinoma cells can be detected on cytologic BM preparations at frequencies of 10-5 to 10-6. Prospective clinical studies have shown that the presence of these immunostained cells is prognostically relevant with regard to relapse-free and overall survival. The current interest in autologous bone marrow transplantation in patients with solid tumors further underlines the need for screening methods that allow the detection of minute numbers of residual tumor cells in the transplant. Although the development of new molecular detection methods based on the amplification of a marker mRNA species by the polymerase chain reaction technique is a very exciting area of research, the clinical significance of this approach needs to be demonstrated in prospective studies. The immunocytochemical assays may be, therefore, used to improve tumor staging with potential consequences for adjuvant therapy. Another promising clinical application is monitoring the response of micrometastatic cells to adjuvant therapies, which, at present, can only be assessed retrospectively after an extended period of clinical follow-up. The extremely low frequency of BM tumor cells greatly hampers approaches to obtain more specific information on their biological properties. The available data indicate that these cells represent a selected population of cancer cells which, however, still express a considerable degree of heterogeneity with regard to the expression of MHC class I antigens, adhesion molecules (EpCAM), growth factor receptors (EGF receptor, erb-B2, transferrin receptor), or proliferation-associated markers (Ki-67, p120). Regardless of the detection technique applied, there is an urgent demand for large multicentre trials, in which standardized methods are related to specified clinical outcomes.     

Clinical significance of proliferative potential of occult metastatic cells in bone marrow of patients with breast cancer

There is increasing statistical evidence that the presence of tumour cells in bone marrow detected by immunocytochemistry represents an important prognostic indicator in breast cancer, but their individual capacity to become clinical metastases is unknown. The aim of this study was to assess the proliferative capacity of these occult metastatic cells in the bone marrow of patients with various stages of breast cancer. We obtained bone marrow aspirates from 60 patients with breast cancer before treatment with chemotherapy: 17 stage II, 12 stage III and 31 stage IV. After bone marrow culture for 6-34 days (median: 17 days) under specific cell culture conditions, viable epithelial cells were detected by cytokeratin staining in 40 patients (66%). Expansion of tumour cells was poorly correlated with tumour cell detection on primary screening (P=0.06). There was a nonsignificant correlation between the number and the presence of expanded tumour cells and the UICC stage of the patients. On primary screening, tumour cell detection was positive in 56% of patients and was correlated with clinical UICC stage (P=0.01). However, with a median follow-up of 23 months, expansion of tumour cells from bone marrow was associated with decreased patient survival (P=0.04), whereas the survival difference according to detection of CK-positive cells on primary screening was not statistically significant. In conclusion, viable tumour cells can be detected in the bone marrow of breast cancer patients. Their proliferative potential could be predictive of outcome and deserves further investigation.     

Immunocytochemical detection of breast cancer cells in marrow and peripheral blood of patients undergoing high dose chemotherapy with autologous stem cell support

Summary Detection of small numbers of breast cancer cells is important in staging the disease and can be helpful in assessing the efficacy of purging regimens prior to autologous stem cell infusion. Immunohistochemical methods are potentially useful and broadly applicable for this purpose since they are simple to perform, sensitive, and may be quite specific. We have used a combination of four monoclonal antibodies [260F9, 520C9, 317G5 (Baxter Corp); BrE-3 (Dr. R. Ceriani)] against tumor cell surface glycoproteins in a sensitive immunocytochemical assay to identify breast tumor cells in bone marrow and peripheral blood. Immunostained cytospin preparations were fixed prior to staining to preserve cytological details of immunopositive cells. After immunostaining, slides were counterstained with hematoxylin to confirm the identity of labeled cells. In cytocentrifuge experiments in which small numbers of CAMA human breast tumor cells were added to bone marrow mononuclear cells, a linear relationship between the number of tumor cells added and the number of tumor cells detected was obtained over a broad range of tumor cell concentrations. The probability of detecting tumor cells was dependent on the number of cytocentrifuge slides examined. When ten slides (5 million cells) were examined, the probability of detecting tumor at a concentration of 4 tumor cells per million bone marrow mononuclear cells was 98%. In clinical specimens, tumor cells were detected in marrow aspirates from 73 of 240 (30%) patients undergoing autologous transplantation, including 70 (37%) of 190 patients with clinical stage IV disease, 0 of 7 patients with clinical stage III disease, and 3 of 43 (7%) patients with clinical stage II disease. Seventy-three of 657 peripheral blood specimens from 26 of 155 patients (17%) contained breast cancer cells with counts ranging from 1 to 97 tumor cells per million leukocytes. Tumor cells were most frequently found in the blood of patients with stage IV disease [21 of 107 (20%)] but were also found in a substantial number [5 of 44 (11%)] of patients with stage II disease. Positive selection of CD34-positive hematopoietic progenitor cells as well as negative purging methods such as incubation with 4-hydroxyperoxy-cyclophosphamide (4-HC) were evaluated with respect to tumor cell depletion. Selection of CD34-positive progenitor cells from bone marrow or peripheral blood resulted in log reduction of 1 to > 4 tumor cells reinfused at autologous transplantation. A lesser log reduction (up to 1) was demonstrated following 4-HC purging. We conclude that properly performed and controlled immunocytochemical staining of bone marrow and peripheral blood cytospins is a sensitive and simple way to detect and quantitate breast cancer cells in hematopoietic specimens harvested for autotransplantation and that CD34-positive progenitor cell selection results in significant reduction in the number of breast cancer cells reinfused with marrow or peripheral blood stem cells.     

Prognostic value of bone marrow biopsy in operable breast cancer patients at the time of initial diagnosis: Results of a 20-year median follow-up

From May 1975 until May 1980, 128 operable breast cancer patients, clinical stage I–II, had a core bone marrow biopsy (BMB) from the posterior iliac crest as a part of the routine diagnostic work-up at the time of initial diagnosis. The mean age of the patients was 56 years, range 26–93. In a previous study on this material, 10 patients (7.8 per cent) were positive for tumor cells and 118 negative by conventional histopathology of BMB [1]. In 1996 we reexamined all BMB separately at two laboratories, using monoclonal antibodies against cytokeratins AE1—AE3, KL1, CAM 5–2 (DOP), and DC10, BA17 (MCI). The number of extrinsic cells in the bone marrow was graded positive for micrometastases when 5 cells or suspicious when 1–4 cells per 2 × 10⁶ bone marrow cells were found, using high power field magnification. Micrometastases were detected in 17 patients (13.3 per cent) and another 8 patients were classified as suspicious. The presence of micrometastases was correlated to the axillary lymph node stage and primary tumor location. Median follow-up was 20 years. All 17 micrometastatic patients relapsed and died within 6 years of disease progression with evident osseous metastases. There was one disease-free survivor of the 8 patients with suspicious BMB after 17 years of follow-up. The median overall survival was significantly shorter in tumor-cell positive patients, being 1.9 years compared to 11.7 years in the BMB negative and BMB suspicious groups (p < 0.0001). Immunohistochemical analysis of core BMB taken postoperatively may be useful in predicting the prognosis in patients with breast cancer clinical stage I–II.This revised version was published online in October 2005 with corrections to the Cover Date.     

Comparison of the clinical significance of occult tumor cells in blood and bone marrow in breast cancer

Immunocytochemical (ICC) detection of disseminated tumor cells (DTC) in bone marrow (BM) in early breast cancer is an independent prognostic factor. The significance of circulating tumor cells (CTC) in peripheral blood (PB) needs further exploration and comparison to DTC detection. PB and BM were prospectively collected from 341 breast cancer patients median 40 months after operation. PB samples were analyzed for tumor cells by a negative immunomagnetic technique (10x10(6) cells/test). BM aspirates were analyzed by standard ICC (2x10(6) cells/test). CTC were present in 10% of the patients and DTC in 14%. Thirty-seven relapses and 14 breast cancer deaths have occurred at median 66 months after diagnosis. Both CTC-status and DTC-status were significantly associated with disease free survival (DFS) (event rate: CTC-positive 26.5% vs. CTC-negative 9.1%; DTC-positive 29.2% vs. DTC-negative 7.8%) (p<0.001/p<0.001, log rank) and breast cancer specific survival (event rate: CTC-positive 17.6% vs. CTC-negative 2.6%; DTC-positive 12.5% vs. DTC-negative 2.7%) (p<0.001/p<0.001). The presence of both CTC and DTC (n=8) resulted in an especially poor prognosis (p<0.001). In node negative patients, DTC-status, but not CTC-status, predicted differences in DFS (p=0.006 vs. p=0.503). Excluding 23 patients with breast cancer-related events prior to the sample collections, CTC detection was not significantly associated with DFS/distant-DFS (p=0.158/0.193), in contrast to DTC detection (p<0.001/<0.001). Presence of CTC and absence of DTC did not affect DFS (p=0.516). Applied to early stage disease, CTC analysis of increased volumes of PB appears less sensitive and prognostic than standard DTC analysis. Currently, this does not support an exchange of BM with PB for analysis of occult tumor cells.     

Detection of cytokeratin-positive cells in the bone marrow of breast cancer patients undergoing adjuvant therapy

Summary The presence of cytokeratin-positive cells in the bone marrow of breast cancer patients has been proven to be an independent prognostic factor. Their fate in primary breast cancer patients undergoing adjuvant therapy is of particular interest. We investigated the bone marrow status of 112 patients undergoing postoperative adjuvant treatment before and after therapy. A total of 373 patients with histologically confirmed primary breast cancer underwent bone marrow aspiration at the time of primary surgery. All patients were informed of their bone marrow status and offered repeat aspiration after 12 months. All patients were then treated with adjuvant chemotherapy, endocrine therapy or both based on current treatment recommendations. About 112 patients returned for a second bone marrow aspiration after a mean interval of 12 months following the initiation of adjuvant treatment. In 93 of 112 patients (83%) disseminated tumor cells had been found in the bone marrow before initiation of systemic chemo/endocrine therapy. At the time of follow-up sampling, after surgery and completion of adjuvant chemotherapy, the positivity rate dropped to 24%. Positive bone marrow status during follow-up was only associated with grading (p=0.020). Adjuvant treatment regimens are not able to completely eliminate cytokeratin-positive cells from the bone marrow. Prospective studies need to evaluate, whether these cells could become targets for additional adjuvant therapy.     

Successful chemo-endocrine therapy for multiple bone metastases and myelophthisis caused by occult breast carcinoma

We report a 55-year-old postmenopausal woman with occult breast carcinoma with multiple bone metastases and myelophthisis in whom complete response (CR) was achieved with chemo-endocrine therapy. At the time of admission, she had anemia and left axillary lymph node enlargement, with extremely high levels of serum tumor markers and no breast mass on physical examination or on a mammogram. Roentgenograms and bone scintigrams showed multiple bone, lung, and pleural metastases. Bone marrow biopsy and aspiration cytology from the left axillary lymph node revealed an invasion of adenocarcinoma cells. On immunohistochemical staining, the cancer cells were positive for estrogen receptor (ER), progesterone receptor (PgR), and gross cystic disease fluid protein-15 (GCDFP-15). CR was induced with a combination chemotherapy of doxorubicin, cyclophosphamide, and 5-fluorouracil (CAF), and has been maintained with sequential docetaxel administration with endocrine therapy. Her performance status (Eastern Cooperative Oncology Group) improved from 4 to 0. This patient represents a very specific and rare case in whom a primary tumor could not be detected despite severe advanced breast carcinoma, and in whom CR was achieved by chemo-endocrine therapy. Received: October 21, 1999 / Accepted: July 28, 2000     

Monoclonal antibodies,benign breast disease,and breast cancer

Hybridoma technology has now advanced to the point where hundreds of monoclonal antibodies have been produced and are reported to bind to normal and malignant cell surfaces or intracellular organelles. The original hope for tumor-specific antigens has not materialized, but certain antibodies with rather restricted ranges of binding activities have been identified. This panel discusses the use of such monoclonal antibodies in diagnosis, prognosis, and treatment of human breast disease and breast cancer.A series of teleconferences has been organized under the auspices of Mead Johnson to address several major current questions in oncology. A panel of recognized experts with a moderator has been assembled to discuss each question, and we will report a number of these discussions in this and succeeding issues of Breast Cancer Research and Treatment. This is reprinted from Oncology Viewpoints, courtesy of Mead Johnson Oncology Division, Evansville IN 47721, USA.     

Differential display analysis of breast carcinoma cells enriched by immunomagnetic target cell selection: gene expression profiles in bone marrow target cells.

The red bone marrow (BM) is an important indicator organ of hematogenous micrometastatic spread of carcinomas. Characterization of biological properties specific for BM micrometastatic cells, however, is technically challenging due to the limited number of target cells usually available for the purpose. This report provides referrals to qualitative gene expression profiling of BM micrometastatic cells enriched by immunomagnetic selection. First, an experimental strategy was used to study regulatory mechanisms involved when BM micrometastatic cells colonize distant organs. The MA-11 cells, originating from BM micrometastases in a breast cancer patient clinically devoid of overt metastatic disease, were injected into immunodeficient rats. Metastatic MA-11 cells were subsequently immunoselected from the resulting in vivo lesions. The selected cell populations were compared to the injected cells by differential display analysis, and several genes possibly involved in tumor cell invasion and proliferation were confirmed as differentially expressed among the various MA-11 cell populations. A direct approach to qualitative gene expression profiling of BM micrometastatic cells was also explored. Carcinoma cells were immunoselected from BM and axillary lymph nodes obtained from breast cancer patients, and the isolated cell populations were compared by differential display analysis. Two candidate genes, identified as factors involved in cellular growth control, appeared as differentially expressed by the target cells from BM. Our study provides detailed information on how to combine an immunomagnetic selection procedure and differential display analysis to reveal gene expression profiles that may characterize BM micrometastatic cells.     

EGFR、C-erbB-2在乳腺癌组织中的表达及其与乳腺癌骨髓微小转移的关系

目的 研究表皮生长因子受体EGFR,C-erbB-2原癌基因在乳腺癌中的表达,探讨其与乳腺癌骨髓微小转移间的关系及对乳腺癌患者预后的影响。方法 选择42例乳腺癌患者石蜡固定的组织标本,用SABC免疫组织化学方法检测EGFR,C-erbB-2蛋白。采用x2检验。结果 EGFR阳性42.9％,C-erbB-2阳性31％。EGFR与C-erbB-2两者间无显著关系。随访患者中,EGFR,C-erbB-2阳性与阴性间术后5年生存率有明显差别。结论 EGFR,C-erbB-2表达与乳腺癌骨髓微小转移有密切关系,可以作为判断乳腺癌预后的重要指标。乳腺癌组织中EGFR,C-erbB-2阳性患者预后不良。     

免疫组织化学和RT-PCR法检测乳腺癌骨髓和前哨淋巴结微小转移的临床研究

目的探讨免疫组织化学(IHC)和RT-PCR法检测乳腺癌骨髓和前哨淋巴结(SLN)微小转移的灵敏度及临床意义。方法留取乳腺癌改良根治术腋窝淋巴结HE染色证实阴性的病人的胸骨骨髓血和SLN,分别采用IHC和RT-PCR方法检测其微小转移情况。结果62例中,骨髓样本RT-PCR检测15例阳性表达,其中9例IHC检测也为阳性,二者结果有较好一致性(kappa=0.6945),检出率有统计学差异(P=0.0412);SLN样本RT-PCR法有13例KT19mRNA表达,其中7例IHC检出KT19阳性细胞,二者结果一致性较好(kappa=0.6483),检出率有统计学差异(P=0.0412);骨髓和SLN同时表达KT19mRNA仅3例,无显著相关(P=0.796);原发肿瘤大小和骨髓KT19mRNA表达率有关联(P=0.003)。结论常规检查未发现远处和腋窝淋巴结转移,骨髓和SLN可检出微小转移,RT-PCR较IHC更灵敏,肿瘤大小与骨髓微小转移有关联。由于骨髓和腋窝淋巴结微小转移不一定同步出现,选用灵敏方法对不同组织同时进行检测可能更具临床价值。     

Disseminated tumor cells in the bone marrow of patients with ductal carcinoma in situ

Detection of disseminated tumor cells (DTCs) in bone marrow is an independent prognostic factor in primary breast cancer. Here, we conducted a proof-of-principle study to evaluate whether this tumor cell spread occurs already in patients with ductal carcinoma in situ (DCIS). After preoperative screening by stereotactic core biopsy, 30 consecutive women with DCIS were included. Bone marrow aspirates, taken at the time of primary surgery, were subjected to DTC detection by a standardized immunoassay using the established monoclonal anti-cytokeratin antibodies A45-B/B3 and AE1/AE3. DTCs were detected in 4 of 19 cases of pure DCIS (21.1%) and in four of seven cases of DCIS with microinvasion (57.1%). After a median follow-up time of 22 months, two initially DTC-positive patients suffered from contralateral carcinoma and contralateral DCIS at months 12 and 30, respectively, whereas the remaining patients were relapse free. Thus, hematogenous tumor cell dissemination into bone marrow is an early event in breast cancer development.     

乳腺癌骨髓微小转移灶的检测与意义

骨是乳腺癌最常见的转移部位之一 ,大约 3 0 %左右的可手术乳腺癌存在骨髓微小转移灶。主要阐述了乳腺癌骨髓微小转移灶的检测方法及其预后意义 ,同时对乳腺癌微小转移灶的生物学特性和对辅助治疗的反应加以综述     

肿瘤特异性CTLs的制备及其对乳腺癌骨髓微转移的治疗效果

目的：制备乳腺癌患者自体肿瘤特异性细胞毒T淋巴细胞（autotumor specific cytotoxicity T lymphocytes,CTLs）,观察其对乳腺癌患者骨髓微转移的治疗作用。方法:以CK18、CK19为标志物、应用流式细胞术检测河北医科大学第四医院外一科2007年3-12月间治疗的82例原发性乳腺癌（Ⅰ～Ⅲ期）术前患者（参加本实验的患者全部知情同意）骨髓微转移状况,将23例术前骨髓微转移阳性的乳腺癌患者随机分为2组：肿瘤特异性CTLs治疗组17例,IL2治疗对照组6例。术中取治疗组患者腋下淋巴结及外周血体外诱导培养肿瘤特异性CTLs,于术后10~14 d回输,观察特异性CTLs对乳腺癌骨髓微转移的治疗效果。结果:本组82例乳腺癌患者中23例（28.05%）骨髓微转移阳性,骨髓微转移的阳性率随临床分期、组织学分级的增加而增高,随 ER、PR 蛋白表达增强而降低。自乳腺癌患者外周血中成功分离、诱导培养出树突状细胞（dendritic cells,DCs）,并经自体肿瘤抗原致敏,与患者腋窝淋巴结来源的淋巴细胞共培养后诱导产生自体肿瘤特异性CTLs。治疗组17例患者经特异性CTLs治疗后,14例转为阴性,转阴率为82.35%;对照组6例中仅1例转为阴性,转阴率为16.67%;肿瘤特异性CTLs的治疗效果显著高于对照治疗（P=000028）。结论:成功制备的肿瘤特异性CTLs对乳腺癌骨髓微转移有较好的治疗效果。     

乳腺癌前哨淋巴结和骨髓和外周血微小转移的联合检测

目的:探讨采用HE染色、免疫组织化学(IHC)和RTPCR等不同方法同时检测乳腺癌前哨淋巴结(SLN)、骨髓和外周血微小转移的灵敏度及其临床意义。方法:全身麻醉后先行骨髓穿刺和外周血采集,选用1%异硫蓝行前哨淋巴结活检(SLNB)后,采用HE染色、IHC和RTPCR等不同方法同时检测乳腺癌SLN、骨髓和外周血的微小转移。结果:腋窝淋巴结常规HE染色病理检查阴性患者38例,4例RTPCR技术和IHC方法检测SLN微小转移同时阳性,另外RTPCR技术还有6例KT19mRNA也表达,两种方法间显著相关,P=0003,但灵敏度上差异无统计学意义,P=0076;骨髓KT19mRNA阳性表达11例,明显高于外周血阳性表达3例,P=0018;RTPCR技术11例骨髓阳性表达,其中6例IHC检测也为阳性,二者间显著相关,P=0000,但灵敏度上差异无统计学意义,P=0169;38例骨髓和SLN中仅2例同时表达KT19mRNA,其间无显著相关,P=0690。结论:即使术前常规检查未发现腋窝淋巴结及远处转移,骨髓、外周血和淋巴结也可检出微小转移灶。由于骨髓和腋窝淋巴结不是同步出现,因此临床上需要检测多种组织、多个指标,才能更精确地对微小转移进行评价。     

Selective growth of freshly isolated human breast epithelial cells cultured at low concentrations in the presence or absence of bone marrow cells

Summary In this study, we show that conditions previously found to promote the selective growth of human breast epithelial cells (HBEC) in serum-free primary cultures established from normal or malignant tissue can be extended to cultures initiated at low seeding densities (< 5000 cells/cm²). The epithelial nature of the cells produced was documented by their positive staining with antibodies specific for keratins 8, 14, and 18, and 2 antibodies that recognize epithelial-specific antigens (Ber-EP4 and HB8630). HBEC growth was not affected, either positively or negatively, by the use of a medium containing a combination of fetal calf and horse serum, which promotes the growth of many types of stromal cells and associated hematopoietic precursors, or by the inclusion in the initial cell suspension of marrow cells at HBEC to marrow cell ratios typical of bone marrow samples from patients with metastatic breast cancer. The presence of fibroblast feeders from a variety of sources enhanced the growth of HBEC to different degrees. In cultures initiated with low numbers of cells obtained from samples of breast carcinoma, HBEC growth was generally reduced by comparison to cultures of normal HBEC. With the detection methods used, it was not possible to determine the extent to which this decreased growth was due to a reduced frequency of malignant HBEC within vitro precursor activity, or the presence of reduced numbers of residual normal HBEC precursors, or both. However, preliminary data indicate that this approach also allows the detection of some breast carcinoma cells with proliferative ability that are present in the marrow or pleural effusions of some breast cancer patients. These studies demonstrate the feasibility of detecting normal and malignant HBEC with growth potential when these are cultured at low density and/or as rare contaminants of marrow cell suspensions, and provide a starting point for their further characterization.     

Clinicopathological value of immunohistochemical detection of occult involvement in pT3N0 gastric cancer

Background. In cases of pT3 gastric cancer, even when standard histological staining reveals no evidence of metastases in the regional lymph nodes, patients still may die of postoperative recurrence of the tumor. An attempt was made in the present study to explain the unfavorable outcome of such patients by investigating the presence of occult cancer cells in lymph nodes by immunostaining of cytokeratin. Methods. We examined 2310 lymph nodes that had been removed from 83 patients with stage II gastric cancer (pT3, N0, M0). Two consecutive sections of 4 μm thick were prepared for simultaneous staining with hematoxylin and eosin and immunostaining with the CAM 5.2 monoclonal antibody against cytokeratin, respectively. Results. Evidence of occult involvement was found in 299 of 2310 (13%) lymph nodes and in 54 of 83 (65%) patients with pT3 gastric cancer. An analysis of survival demonstrated the limited 5-year survival of patients with occult involvement in their resected lymph nodes, as compared with that of patients without involvement (P < 0.01). Moreover, the patients in whom group 2 lymph nodes had occult cancer cells had a significantly poorer prognosis than those in whom occult involvement was limited to group 1 lymph nodes (P < 0.05). Conclusions. The accuracy of predictions of prognosis of patients with pT3 gastric cancer should be greatly enhanced if cytokeratin-specific immunostaining is performed in conjunction with routine histopathological examination of lymph nodes. Received for publication on Dec. 24, 1998; accepted on March 31, 1999     

乳腺癌骨转移放射治疗临床分析(附32例报告)

目的　探讨乳腺癌骨转移的临床特点及放射治疗效果。方法　回顾分析 3 2例乳腺癌骨转移资料 ,转移灶单发 10例 ,多发 2 2例 ,共 68处病灶 ,其中脊柱占 2 7 9% ,骨盆占 2 2 1% ,肋骨占 13 2 %、股骨占10 3 % ,其余依次为肱骨、颅骨、肩胛骨、胫骨、锁骨。 2 2例行放射治疗 ,放疗前中度疼痛 17例 ,重度疼痛 5例 ,6例功能障碍。结果　 2 2例治疗后完全缓解 16例 ,部分缓解 6例 ,卡氏评分有所改善 ,功能障碍均恢复 ,治疗后的 1、2、3年生存率分别为 5 9 1%、2 2 7%、4 5 % ,中位生存期 15月 ,而未治组 10例的中位生存期为 4 5月 (P <0 0 1)。结论　乳腺癌骨转移行放射治疗 ,止痛作用快而持久 ,提高了患者的生存质量 ,是一种简单有效的治疗方法