The natural course of cutaneous melanoma

The natural course of cutaneous melanoma (CM) is determined by its metastatic spread and depends on tumor thickness, ulceration, gender, localization, and the histologic subtype of the primary tumor. CM metastasis develops via three main metastatic pathways and occurs as satellite or in-transit metastasis, as regional lymph node metastasis or as distant metastasis at the time of primary recurrence. About 50% of all CM patients with tumor progression firstly develop regional lymph node metastases. In the other 50% the first metastases are satellite or in-transit metastases (about 20%), or immediately distant metastases (about 30%). Development of distant metastasis appears to be an early event in metastatic spread and may in the majority of cases originate from the primary tumor, only few cases may develop secondarily to locoregional metastasis. Reporting of organ involvement in distant metastasis greatly differs between the results of imaging techniques and autopsy results in respect to the metastatic patterns detected, pointing out that there is a need of improved imaging systems. Proliferation, neovascularization, lymphangiogenesis, invasion, circulation, and embolism are important steps in the pathogenesis of CM metastasis, with tumor vascularity as an important independent significant prognostic factor. The expression of chemokine receptors in cancer cells associated with the expression of the respective chemokine receptor ligands in the target sites of the metastasis is an interesting observation which may stimulate the development of new therapeutic strategies.     

Reduced KAI1 expression in pancreatic cancer is associated with lymph node and distant metastases

KAI1 belongs to a structurally distinct family of membrane glycoproteins, which function via cell-cell and cell-extracellular matrix interactions, thereby potentially influencing the ability of cancer cells to invade tissues and to metastasize into lymph nodes and distant organs. In the present study, we examined KAI1 expression in lymph node and liver metastases in comparison with primary pancreatic cancer to evaluate its influence on metastasis. KAI1 mRNA analysis was performed by Northern blot analysis and in situ hybridization. In addition, the respective protein was studied by immunostaining. Fourteen primary pancreatic cancer samples in which no lymph node metastases were present and 25 primary pancreatic cancer samples in which lymph node metastases were present at the time of tumor resection were included. In 20 of these cases, primary pancreatic cancer tissues and corresponding lymph node metastases from the same patient were studied. Furthermore, 11 liver metastases were available for KAI1 analysis. Increased steady-state levels of KAI1 mRNA were found in 33/39 (85%) primary pancreatic cancers in comparison with normal controls. Statistical analysis of KAI1 mRNA levels and clinical parameters of the patients revealed that KAI1 mRNA levels were significantly higher in non-metastasized tumors compared with tumors in which lymph node or distant metastases were present. In lymph node metastases KAI1 mRNA expression was lower than in the corresponding primary tumors: In 14 of 20 lymph node metastases no KAI1 mRNA expression and in 6 of 20 lymph node metastases only weak KAI1 mRNA levels were present in some cancer cells. Cancer cells of distant metastases were devoid of or exhibited low KAI1 mRNA levels compared with those of primary pancreatic cancers. A similar pattern was observed by immunostaining. These data support the hypothesis that KAI1 gene expression might influence the metastatic ability of pancreatic cancer cells in vivo. Reduction of KAI1 appears to promote cancer cell spread in lymph nodes and distant organs. Int. J. Cancer (Pred. Oncol.) 79:349–355, 1998. © 1998 Wiley-Liss, Inc.     

乳腺癌原发灶与转移灶分子分型指标表达差异的研究

目的 乳腺癌患者激素受体(hormone receptor,HR)、人类表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)和增殖细胞核抗原Ki-67的表达状态直接影响治疗方案的制订.本研究通过比较可手术乳腺癌原发灶与腋窝淋巴结转移灶及治疗后远处转移灶之间HR、HER2和Ki-67表达状况,探讨其表达的一致性,以期为乳腺癌患者综合治疗方案的制订提供参考.方法 选取2015-03-01-2016-04-30就诊于山东大学附属山东省肿瘤医院(162例)和梁山县人民医院(23例)的185例乳腺癌患者作为研究对象.患者均为女性,年龄24～79岁,中位年龄49岁.浸润性导管癌171例,浸润性小叶癌14例.初治直接接受手术治疗患者110例,其中有腋窝淋巴结转移77例;复发转移患者接受转移灶穿刺患者75例,其中肝脏转移43例,肺脏转移32例.所有标本均检测ER、PR、HER2和Ki-67表达,比较原发灶与腋窝淋巴结及远处转移灶的表达情况.结果 原发灶与腋窝淋巴结转移灶ER、PR、HER2和Ki-67表达差异均无统计学意义(均P＞0.05),ER变化率为3.9％,PR为7.8％,HER2为11.7％,Ki-67为20.8％.原发灶与远处转移灶比较,PR和Ki-67表达差异有统计学意义(均P值＜0.05),而ER和HER2表达差异无统计学意义(均P＞0.05),ER变化率为21.3％,PR为29.3％,HER2为18.7％,Ki-67为29.3％.结论 乳腺癌原发灶与转移腋窝淋巴结ER、PR、HER2和Ki-67表达状况一致性较高;原发灶与远处转移灶PR和Ki-67的表达存在差异,ER和HER2的表达无差异,这可能受多种因素的影响,建议对原发灶及转移灶同时进行生物学信息的检测,为患者制订治疗方案提供可靠的生物学信息.     

Molecular factors of 5-fluorouracil metabolism in colorectal cancer: analysis of primary tumor and lymph node metastasis

Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP) are predictive markers for tumor response to 5-fluorouracil-based therapies. To determine whether gene expression values measured in primary cancer tissue would be useful for prediction of response of lymph node metastases, the expressions of these genes were quantitatively analyzed in 35 pairs of primary colorectal cancer (CRC) and corresponding lymph node metastases using real-time PCR. DPD and TP mRNA levels were significantly lower in the primary colorectal tumor and lymph node metastases compared with the normal adjacent stroma tissue (p<0.01), whereas TS mRNA levels were significantly higher in the primary tumor and lymph node metastases than in the normal adjacent tissue (p<0.001). Median gene expression levels of TP and TS did not differ significantly between primary colorectal tumor and corresponding lymph node metastasis but median DPD gene expression levels in the lymph node metastases were significantly higher compared to matched primary colorectal tumors (p=0.015). There was a significant correlation for DPD, TP and TS gene expression levels between primary colorectal tumor specimens and the matched lymph node metastasis. These results suggest that biopsies of the tumor of origin may be valid for determining predictive markers for chemotherapy response in patients with metastatic CRC.     

Correlation between genetic and biological aspects in primary non-metastatic breast cancers and corresponding synchronous axillary lymph node metastasis

This study investigated the changes, if any, in the level of expression of a well defined panel of cell proliferation, differentiation and apoptosis markers between the primary breast tumor and the corresponding synchronous lymph node metastasis from a population of patients with a comparable disease status, in terms of clinical features, and natural history. Ninety pure invasive ductal carcinomas with 10 or more axillary lymph nodes involved and without evidence of distant metastasis were included in this study. Primary tumor and corresponding metastatic lymph node tissue specimens were evaluated for the expression of Cyclin B1, MMP1 metalloproteinase, ICAM-1, RARβ, Ki67, ER, PgR, p53, bcl-2 and c-erbB2 by immunohistochemistry using standard methods. The bivariate Pearson correlation analysis demonstrated a close relationship between primary and matching corresponding metastatic node. A high grade of correlation has been maintained even when staining results where categorized as positive/negative according to each one marker cut-off level of staining expression. We report the most extensive immunohistochemical analysis of biological determinants in a well defined population of patients with invasive ductal carcinomas and involvement of 10 or more axillary nodes and no distant metastasis. We found a close correlation between the primary tumor and corresponding metastatic node in terms of the expression of all 10 of the markers investigated in this study. The not complete concordance observed could be explained by the gene expression modulation by extrinsic factors and by the microenvironment in which the cancer cells reside.     

Differentially expressed genes between primary cancer and paired lymph node metastases predict clinical outcome of node-positive breast cancer patients

The axillary lymph node status remains the most valuable prognostic factor for breast cancer patients. However, approximately 20-30% of node-positive patients remain free of distant metastases within 15-30 years. It is important to develop molecular markers that are able to predict for the risk of distant metastasis and to develop patient-tailored therapy strategies. We hypothesize that the lymph node metastases may represent the most metastatic fraction of the primary cancers. Therefore, we sought to identify the differentially expressed genes by microarray between the primary tumors and their paired lymph node metastases samples collected from 26 patients. A set of 79 differentially expressed genes between primary cancers and metastasis samples was identified to correctly separate most of primary cancers from lymph node metastases. And decreased expression of matrix metalloproteinase 2, fibronectin, osteoblast specific factor 2, collagen type XI alpha 1 in lymph node metastases were further confirmed by real-time RT-PCR performed on 30 specimen pairs. This set of genes also classified 35 primary cancers into two groups with different prognosis: "high risk group" and "low risk group." Patients in "high risk group" had a 4.65-fold hazard ratio (95% CI 1.02-21.13, P = 0.047) to develop a distant metastasis within 43 months comparing with the "low risk group." This suggested that the gene signature consisting of 79 differentially expressed genes between primary cancers and lymph node metastases could also predict clinical outcome of node-positive patients, and that the molecular classification based on the gene signature could guide patient-tailored therapy.     

Staging of head and neck squamous cell carcinoma using the MET oncogene product as marker of tumor cells in lymph node metastases

In head and neck squamous cell carcinomas (HNSCC), metastasis to cervical lymph nodes is a major determinant of patient outcome. To detect metastases, we used the MET oncogene as marker, which encodes the receptor for hepatocyte growth factor/scatter factor, mediating epithelial cell motility and invasiveness. The MET gene is expressed in epithelia and over-expressed in carcinomas of specific histotypes, but not in lymphatic tissue. A total of 151 lymph nodes from 20 squamous cell carcinomas were studied with both in-depth histology and end-point and real-time quantitative RT-PCR. MET-encoded sequences were found in 61 of 151 nodes (40%), of which 24 (16%) were found metastatic by in-depth histopathology. Parallel routine histopathologic analysis of 654 lymph nodes from the same cases identified 36 metastases (5%). Real-time quantitative RT-PCR was used to measure MET gene-specific mRNA in normal tissues, primary tumors and lymphatic metastases and showed a 2-8-fold increased expression in tumor cells which metastasize. RT-PCR for 3 cytokeratins expressed in HNSCC (K4, K10 and K13) proved to be less sensitive in detecting occult lymphatic metastases. Western blot analysis demonstrated the presence of the full-size MET receptor in primary tumors and lymph node metastases; immunohistochemistry showed receptor localization in tumor cells. Altogether, these data demonstrate that the MET gene product is a valuable marker with which to detect occult tumor cells in lymph nodes, thanks to its high expression in metastatic cells. After RT-PCR analysis we were able to attribute a more advanced stage to 10 out of 20 HNSCC cases, including 5 cases classified as tumor-free after routine histopathology.     

Tumor-associated antigen TAG-72: Correlation of expression in primary and metastatic breast carcinoma lesions

Variability of tumor-associated antigens among and within human tumor cell groups presents a potential problem in the development and optimization of immunodiagnostic and therapeutic procedures for cancer. We determined the degree of expression of a tumor-associated antigen in the primary and metastatic lesions of 23 patients with infiltrating ductal carcinoma; this was accomplished using monoclonal antibody B72.3, an IgG1 generated against membrane-enriched fractions of human metastatic breast carcinomas and reactive with a 220,000-400,000 d glycoprotein complex, termed TAG-72, and the avidin-biotin complex immunoperoxidase method on fixed tissue sections. Sixteen of the 23 breast carcinomas (70%) demonstrated MAb B72.3 reactivity (range 5% to 100% of tumor cells staining). Reactivity of lymph node metastases was present in 14 of 21 patients (67%). MAb reactivity in metastases to distant sites, including bone, adrenals, liver, skin and effusions, was present in 10 of 18 patients (56%). In one patient, neither the primary carcinoma nor the metastasis to the lymph node demonstrated reactivity. There was a statistically significant positive correlation between MAb B72.3 reactivity in both primary and lymph node metastases (Kendall's Correlation Coefficient = 0.60, p = 0.0006) and between lymph node and distant metastases (Kendall's Correlation Coefficient = 0.48, p = 0.02) of the same patient. No correlation existed between antibody reactivity seen in the primary and that found in the distant lesions of that patient. These studies thus demonstrate that monoclonal antibody B72.3 can detect expression of a tumor-associated antigen in both primary and metastatic infiltrating ductal carcinoma lesions, and may prove valuable in the understanding of tumor biology of metastases and as a means for diagnosing occult disease.     

The loss of E-cadherin, alpha- and beta-catenin expression is associated with metastasis and poor prognosis in invasive breast cancer

Loss of E-cadherin and catenin expression may be associated with distant and lymph node metastases in breast cancer. Heterogeneity of E-cadherin expression is associated with poor prognosis, suggesting that E-cadherin and catenins may serve as useful prognostic markers for invasive breast carcinoma. Reduction or loss of expression of either E-cadherin or catenins is associated with invasion, metastasis and poor prognosis in several types of human malignancies. We investigated the expression of E-cadherin, and alpha- and beta-catenins by immunohistochemistry in 171 cases of primary invasive breast cancer, and compared the expression with clinicopathological parameters to define the relationship between expression and prognosis. E-cadherin immunoreactive protein was shown to be expressed in 97 cases. Reduction or lack of expression of E-cadherin was associated with distant metastasis. Based on immunohistochemical heterogeneity, E-cadherin-positive tumors were classified into heterogeneous, homogeneous and intermediate types. Interestingly, although patients with heterogeneous type demonstrated the lowest incidence of distant metastasis at diagnosis, they showed a higher incidence of subsequent distant metastasis, after surgery, and a lower survival rate than those with homogeneous type (p<0.05). E-cadherin expression was reduced or negative in metastatic axillary lymph nodes regardless of the expression in the primary tumor, suggesting that changes in E-cadherin expression are associated with not only distant metastasis but also lymph node metastasis. Tumors negative for either alpha- or beta-catenin expression demonstrated a higher incidence of distant metastasis than those expressing both catenins, suggesting that the expression of catenins is involved in breast cancer metastasis. Reduction or loss of E-cadherin and catenin expression may be associated with distant and lymph node metastases in invasive breast cancer, and the heterogeneous type may be associated with poor prognosis.     

From tumor lymphangiogenesis to lymphvascular niche

Metastasis in sentinel lymph nodes indicates the initial spread of tumors from a primary site. The recent discovery of tumor-associated growth of lymphatic vessels clarified that tumor lymphangiogenesis actively promotes enhanced draining/sentinel lymph node metastasis. Studies of experimental carcinogenesis have further established that tumors continue to induce lymphangiogenesis in metastatic foci such as draining lymph nodes. Lymphangiogenesis within draining lymph nodes probably contributes to enhanced distant lymph node and distant organ metastases. Lymph node lymphangiogenesis has recently been identified in several human malignancies, such as cutaneous malignant melanoma. Tumor-associated lymphangiogenesis thus has potential significance not only at the primary site, but also in lymph nodes. Primary tumors induce new lymphatic vessel growth in draining lymph nodes before metastasis. The remarkable enlargement of sinusoidal lymphatic endothelium might facilitate tumor cell transport to the lymph nodes, and potentially contribute to the migration, residence, and/or survival of metastatic tumor cancer stem cells by inducing a specific tumor microenvironment. Therefore, the novel concept of 'lymphvascular niche' is proposed herein to explain lymphatic network expansion. This concept might help to improve understanding of the molecular mechanism of lymph node metastasis, and change therapeutic approaches to treating cancer metastasis. ( Cancer Sci 2009; 100: 983–989)     

Mouse model of postsurgical primary tumor recurrence and regional lymph node metastasis progression in HPV‐related head and neck cancer

HPV‐positive head and neck squamous cell carcinoma (HNSCC) is increasingly frequent. Management is particularly debated in the case of postsurgical high‐risk features, that is, positive surgical margins and extracapsular spread (ECS). In this increasingly complex emerging framework of HNSCC treatment, representative preclinical models are needed to support future clinical trials and advances in personalized medicine. Here, we present an immunocompetent mouse model based on the implantation of mouse tonsil epithelial HPV16‐E6/E7‐expressing cancer cells into the submental region of the floor‐of‐the‐mouth. Primary tumors were found to replicate the patterns of human HNSCC local invasion and lymphatic dissemination. To study disease progression after surgery, tumors were removed likely leaving behind residual disease. Surgical resection of tumors was followed by a high rate of local recurrences (>90%) within the first 2–3 weeks. While only 50% of mice had lymph node metastases (LNM) at time of primary tumor excision, all mice with recurrent tumors showed evidence of LNM. To study the consecutive steps of LNM progression and distant metastasis development, LNs from tumor‐bearing mice were transplanted into naïve recipient mice. Using this approach, transplanted LNs were found to recapitulate all stages and relevant histological features of regional metastasis progression, including ECS and metastatic spread to the lungs. Altogether, we have developed an immunocompetent HPV‐positive HNSCC mouse model of postsurgical local recurrence and regional and distant metastasis progression suitable for preclinical studies.     

胸段食管癌的淋巴结转移规律及其对确定术后放射治疗靶区范围的价值

目的 分析胸段食管癌淋巴结转移的规律及其影响因素,探讨食管癌术后放疗的靶区范围.方法 收集763例接受根治性切除的胸段食管癌患者的临床病理资料,分析淋巴结转移规律及影响因素.结果 763例胸段食管癌患者共清除淋巴结5846枚,病理证实转移711枚,转移度为12.2%;出现淋巴结转移者297例,转移率为38.9%.胸上段癌淋巴结转移率为28.5%,明显低于胸中段癌(38.8%)和胸下段癌(43.4%).胸上段癌以锁骨上和气管旁淋巴结的转移度和转移率最高.胸中段癌的上行和下行转移均存在,上行主要转移至锁骨上、气管旁和食管旁,下行主要转移至贲门和胃左动脉旁.胸下段癌则主要向食管旁、贲门和胃左动脉旁转移,其中胃左动脉旁的转移度和转移率均显著高于胸上段癌和胸中段癌(均P<0.01).采取左胸单切口的592例患者中,胸上、中、下段癌的淋巴结转移率分别为37.0%、37.9%和41.4%,差异无统计学意义(P=0.715).多因素Logistic回归分析表明,病变长度、浸润深度、脉管瘤栓和远处转移是影响胸段食管癌淋巴结转移的主要因素(均P<0.05).结论 临床上可以根据食管癌的病变长度、浸润深度、脉管瘤栓和远处转移选择需行术后预防照射的患者,根据不同病变部位、不同手术方式及TNM分期,确定术后预防照射的靶区范围.     

上皮细胞黏附分子表达与乳腺癌淋巴结转移的相关性

目的 探讨上皮细胞黏附分子(Ep-CAM)在乳腺癌中的表达及意义.方法 收集经病理学确诊的乳腺癌新鲜组织标本23例及配对的淋巴结转移灶.应用同位素标记的相对和绝对定量(iTRAQ)蛋白质组学技术筛选及鉴定乳腺癌原发灶和淋巴结转移灶的差异表达蛋白,在4例新鲜乳腺癌原发灶组织和配对淋巴结转移灶中进行Western blotting检测Ep-CAM的表达.采用免疫组织化学法检测252例乳腺病变标本中Ep-CAM的表达.结果 定量蛋白质组学检测结果显示乳腺癌原发灶和淋巴结转移灶存在差异表达蛋白,其中Ep-CAM在转移灶的表达高于原发灶,Western blotting显示Ep-CAM在转移灶的表达(1.46±0.22)高于原发灶(1.16±0.09),变化趋势与蛋白质组学结果一致.免疫组织化学检测结果显示,Ep-CAM在淋巴结转移灶中的阳性表达率(93.16％,109/117)显著高于无淋巴结转移的乳腺癌原发灶(72.73％,64/88),差异有统计学意义(x2=15.921,P=0.000);有淋巴结转移的乳腺癌原发灶Ep-CAM阳性表达率为72.65％(85/117),较配对淋巴结转移灶阳性表达率低,差异有统计学意义(P=0.001).结论 Ep-CAM在乳腺癌原发灶和淋巴结转移灶呈差异表达,该蛋白可能与乳腺癌淋巴结转移有关.     

CCR7 and CXCR4 Expression in Primary Head and Neck Squamous Cell Carcinomas and Nodal Metastases – a Clinical and Immunohistochemical Study

Background: Squamous cell carcinomas (SCCs) are common head and neck malignancies demonstrating lymph node LN involvement. Recently chemokine receptor overxpression has been reported in many cancers. Of particular interest, CCR7 appears to be a strong mediator of LN metastases, while CXCR4 may mediate distant metastases. Any relations between their expression in primary HNSCCs and metastatic lymph nodes need to be clarified. Aims: To investigate CCR7 andCXCR4 expression in primary HNSCCs of all tumor sizes, clinical stages and histological grades, as well as involved lymph nodes, then make comparisons, also with control normal oral epithelium. Materials and Methods: The sample consisted of 60 formalin-fixed, paraffin-embedded specimens of primary HNSCCs, 77 others of metastasi-positive lymph nodes, and 10 of control normal oral epithelial tissues. Sections were conventionally stained with H&E and immunohistochemically with monoclonal anti-CCR7 and monoclonal anti-CXCR4 antibodies. Positive cells were counted under microscopic assessment in four fields (X40) per case. Results: There was no variation among primary HNSCC tumors staining positive for CCR7 and CXCR4 with tumor size of for CCR7 with lymph node involvement. However, a difference was noted between primary HNSCC tumors stained by CXCR4 with a single as compared to more numerous node involvement. CXCR4 appear to vary with the clinical stagebut no links were noted with histological grades. Staining for primary HNSCC tumors and metastatic lymph nodes correlated.     

Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression

The prognostication of head and neck squamous cell carcinoma (HNSCC) is largely based upon the tumor size and location and the presence of lymph node metastases. Here we show that gene expression patterns from 60 HNSCC samples assayed on cDNA microarrays allowed categorization of these tumors into four distinct subtypes. These subtypes showed statistically significant differences in recurrence-free survival and included a subtype with a possible EGFR-pathway signature, a mesenchymal-enriched subtype, a normal epithelium-like subtype, and a subtype with high levels of antioxidant enzymes. Supervised analyses to predict lymph node metastasis status were approximately 80% accurate when tumor subsite and pathological node status were considered simultaneously. This work represents an important step toward the identification of clinically significant biomarkers for HNSCC.     

Heterogeneous expression and association of beta-catenin, p16 and c-myc in multistage colorectal tumorigenesis and progression detected by tissue microarray

Most colorectal carcinomas (CRCs) arise from adenomas through an archetypal pathogenic pathway, the adenoma-carcinoma-metastasis sequence. Aberrant expression of beta-catenin, p16, E-cadherin and c-myc appears to have played important roles in the development and/or progression of CRC, but their precise distribution pattern and associations in different pathologic loci along CRC's pathogenic pathway have not been thoroughly examined. In this study, a tissue microarray (TMA) containing 85 advanced CRCs in different Dukes stages was constructed. In each of 85 cases, tissue specimens from normal mucosa and primary carcinomas in different layers of the bowel wall were included in the TMA. Tissue specimens from matched adenoma, lymph node metastases and distant metastases were obtained from 22, 21 and 21 cases, respectively. Expression patterns of beta-catenin, p16, E-cadherin and c-myc were evaluated by immunohistochemistry. The results revealed that nuclear expression of beta-catenin, p16 and c-myc was quantitatively increased from normal mucosa to premalignant adenoma, primary carcinoma and lymph node metastatic carcinoma; the frequency of nuclear overexpression of beta-catenin and p16 in lymph node metastases was significantly higher than that in distant metastases (p < 0.05). These results suggest an association between nuclear overexpression of beta-catenin and/or p16 and CRC lymph node metastasis but not distant metastasis. The results also showed that correlative high nuclear expression of beta-catenin and c-myc was observed in primary carcinomas involving the serosa and lymph node metastases (p < 0.05) but not in other pathologic regions of CRCs, suggesting that the tumor microenvironment in different pathologic loci of colorectal tumorigenesis and progression may influence c-myc responsiveness to beta-catenin/Tcf activation.     

Expression of glycodelin protein and mRNA in human ductal breast cancer carcinoma in situ, invasive ductal carcinomas, their lymph node and distant metastases, and ductal carcinomas with recurrence

Glycodelin, previously known as PP14, has been localized in endometrial, ovarian and cervical carcinoma cells. Recently, glycodelin was demonstrated to be expressed in cancerous human breast tissue. In this study, paraffin-embedded slides of carcinoma in situ, invasive carcinomas without metastases, invasive carcinomas with corresponding lymph node metastases, invasive carcinomas with corresponding recurrence and invasive carcinomas with corresponding distant metastases were investigated for glycodelin protein and mRNA expression. Protein expression was found in all cases of carcinoma in situ, in invasive carcinoma without lymph node metastases in 90% of cases, in breast cancer with lymph node metastases in 50% of cases, in breast cancer with recurrence in 38% of cases and in breast cancer with distant metastases in 40% of cases. Results were confirmed by in situ hybridization showing reduced glycodelin expression as lymph node metastasis progressed, compared to carcinoma in situ. Glycodelin mRNA expression is not further reduced in carcinomas with distant metastasis and recurrence compared to carcinoma in situ. Results demonstrate that invasive breast carcinomas without metastases are more likely to express glycodelin. In contrast, cases of breast cancer with metastatic infiltration and recurrence show weak expression of glycodelin. On the basis of these results, we speculate that glycodelin could be used as a prognostic marker for breast cancer.     

肿瘤转移抑制基因KAI1在大肠癌进展中的作用

背景与目的:对于肿瘤转移抑制基因KAI1在大肠癌中的表达及其与病理分期的关系存有争议,关于它与肿瘤患者预后的报道仍然较少。本研究旨在探讨KAI1在大肠癌进展中的作用及其在预后判断中的价值。方法:采用免疫组化法检测91例大肠癌原发灶及25例淋巴结转移灶中KAI1表达。结果:KAI1在大肠癌原发灶中阳性表达54例(59.3%),弱阳性22例(24.2%),阴性15例(16.5%)。KAI1在低分化、有淋巴结转移、远处脏器转移肿瘤中表达显著降低(P<0.01);5年生存者的KAI1阳性表达率(67.14%)显著高于5年内死亡者(33.33%)(P<0.05);KAI1表达阳性、弱阳性以及阴性患者的5年生存率依次为87.04%、63.34%、60.00%,呈下降趋势(P<0.05),淋巴结转移灶的KAI1表达显著低于原发灶(P<0.05)。结论:KAI1的异常表达可能参与了大肠癌的恶性进展。检测KAI1的表达对判断肿瘤的分化、淋巴结转移和远处转移及大肠癌患者预后有一定的参考价值。