乳腺浸润性导管癌中ER、PR、Her-2、Ki-67表达与病理特征及预后的相关性

目的 探究Ki-67、ER、PR、Her-2等基因在乳腺浸润性导管癌（IDC）组织中的表达,分析其与患者临床病理特征及预后的相关性。方法 收集2013年1月~2014年12月广东医科大学附属医院病理科乳腺包埋石蜡块IDC组织74例。采用免疫组织化学法检测ER、PR、Her-2、Ki-67在IDC组织中的表达,分析其与患者年龄、组织学分级、TNM分期、淋巴结转移及预后的相关性。结果 ①不同年龄、组织学分级、淋巴结转移及TNM分期的IDC患者ER、PR表达情况比较,差异均无统计学意义（P＞0.05）;未发生淋巴结转移的IDC患者Her-2表达低于转移患者,差异有统计学意义（P＜0.05）;不同年龄、组织学分级、TNM分期的IDC患者Her-2表达比较,差异无统计学意义（P＞0.05）;不同TNM分期的IDC患者Ki-67表达情况比较,差异有统计学意义（P＜0.05）,不同年龄、组织学分级、淋巴结转移的IDC患者Ki-67表达比较,差异均无统计学意义（P＞0.05）。 ②Spearman相关性分析显示,ER与PR正相关,ER与Her-2、PR与Her-2负相关,ER、Ki-67和PR、Ki-67负相关,Her-2与Ki-67正相关。③Ki-67阳性表达的IDC患者病死率高于Ki-67阴性表达的患者,差异有统计学意义（P＜0.05）;不同ER、PR、Her-2表达情况的IDC患者病死率比较,差异无统计学意义（P＞0.05）;Ki-67阴性表达患者的总生存时间（OS）高于阳性表达患者,COX多因素分析显示,Ki-67阳性表达是影响IDC患者OS的独立因素（95%CI:0.212~0.865,P=0.018）。结论 Ki-67可作为乳腺浸润性导管癌危险评估的分子标志物,其阳性表达可影响乳腺癌患者的预后。ER、PR、Her-2的表达对乳腺浸润性导管癌患者的预后没有明显影响。     

Lymphangiogenesis in Breast Cancer Correlates with Matrix Stiffness on Shear-Wave Elastography

PurposeTo correlate tumor stiffness and lymphangiogenesis in breast cancer and to find its clinical implications.ResultsHigher elasticity value was associated with invasive size of tumor, microlymphatic density, histologic grade 3, absence of extensive intraductal component, presence of axillary lymph node metastasis, and Ki-67 labeling index (LI) in univariate regression analysis, and associated with Ki-67 LI and axillary lymph node metastasis in multivariate regression analysis. Microlymphatic density was associated histologic grade 3, mean elasticity value, and Ki-67 LI in univariate regression analysis. In multivariate regression analysis, microlymphatic density was correlated with mean elasticity value.ConclusionIn breast cancer, tumor stiffness correlates with lymphangiogenesis and poor prognostic factors.     

乳腺癌组织中uPA、uPAR及nm23-H1的表达

目的　观察乳腺癌组织中uPA、uPAR、nm2 3 H1的表达并探讨与腋窝淋巴结转移的关系。方法　用免疫组化EnVi sion两步法检测 6 9例乳腺癌组织中uPA、uPAR和nm2 3 H1表达的分布情况 ,观察其与肿瘤的分化程度以及与腋窝淋巴结转移的关系。结果　 (1)uPA阳性表达定位于癌细胞胞质 ;uPAR和nm2 3 H1阳性表达定位于癌细胞胞膜及胞质 ,多数癌旁乳腺上皮细胞呈nm2 3 H1阳性表达 ;高分化乳腺癌 (Ⅰ级 )uPA和uPAR表达阳性率 (30 0 %和 2 5 0 %)低于中低分化乳腺癌 (Ⅱ、Ⅲ级 ) (分别为 6 8 1%、72 7%和 70 0 %、74 1%) (P <0 0 5 ) ;nm2 3 H1表达阳性率在乳腺癌组织不同分化程度间差异无显著性 (P >0 0 5 ) ;(2 )腋窝淋巴结有转移者uPA和uPAR的表达阳性率 (73 2 %和 75 6 %)高于无淋巴结转移者 (35 7%和35 7%) (P <0 0 5 ) ;有腋窝淋巴结转移者nm2 3 H1的表达阳性率 (2 4 4 %)显著低于无淋巴结转移者 (5 0 0 %) (P <0 0 5 ) ;uPA、uPAR和nm2 3 H1的表达与淋巴结转移的个数均无关 ;(3)uPA阳性表达的癌组织其nm2 3 H1表达阳性率 (15 0 %)低于uPA阴性表达的癌组织 (6 2 1%) (P <0 0 5 )。结论　uPA和uPAR的高表达与乳腺癌腋窝淋巴结转移密切相关 ;uPA、uPAR和nm2 3 H1可以作为乳腺癌侵袭与淋巴结转移的     

Mucin antigens expression and Ki-67 labeling in breast cancer: The peculiarity in scirrhous carcinoma

The expression of mucin-related antigens (Tn, T, Sialosyl-Tn [STn], DF3 [mammary-type apomucin related antigen], and intestinal-MRP [intestinal-type apomucin related antigen]) as well as Ki-67 labeling was examined in 58 mammary invasive ductal carcinomas (IDC) divided into 26 scirrhous subtype (SC) and 32 non-scirrhous subtype comprising papillotubular carcinoma and solid-tubular carcinoma (PT-ST). These data were analyzed in connection with the various pathological prognostic factors such as nodal status, tumor size, estrogen receptor status and histological grading of carcinomas. The results were as follows: (a) in SC, the expression rate of Tn was significantly higher in the cases with positive lymph node metastasis or with large tumor size (>2cm) than in those with negative lymph node metastasis or with small tumor size (>2 cm); (b) in PT-ST, the expression rate of STn was higher in the cases with positive lymph node metastasis or with large tumor size than in those with negative lymph node metastasis or with small tumor size; (c) in SC, Ki-67 labeling was significantly higher in the cases with positive lymph node metastasis than in those with negative lymph node metastasis; and (d) in PT-ST, Ki-67 labeling was lower in the cases with positive lymph node metastasis than in those with negative lymph node metastasis. In conclusion, Tn antigen expression was correlated with pathological prognostic factors in SC but not in PT-ST, whereas STn antigen expression was correlated with pathological prognostic factors in PT-ST but not in SC. Moreover, lnverse relationship between Ki-67 labeling and nodal status was observed in PT-ST. These differences between SC and PT-ST may be related to their different biological behaviors.     

p53,Ki-67及E-钙黏蛋白在三阴性乳腺癌中的表达及预后

目的:探讨p53,Ki-67及E-钙黏蛋白(E-cadherin)在三阴性乳腺癌(triple negative breast cancer,TNBC)组织中的表达及预后的关系.方法:采用免疫组织化学法检测52例TNBC和52例非三阴性乳腺癌(non-triple-negative breast cancer,NTNBC)组织中p53,Ki-67及E-cadherin表达情况,观察3个指标与TNBC患者临床病理学特征及预后的关系.结果:TNBC组织中p53,Ki-67及E-cadherin的阳性表达率分别为67.3％,80.8％,26.9％;而在NTNBC组织中为44.2％,61.5％,48.1％(均P＜0.05).在TNBC组织中,p53表达阳性与肿瘤大小、TNM分期及组织学分级有关(均P＜0.05);Ki-67表达阳性与TNM分期、淋巴结转移有关(均P＜0.05);E-cadherin表达阳性与肿瘤大小、TNM分期、淋巴结转移有关(均P＜0.05).在TNBC患者中,p53,Ki-67及E-cadherin表达阳性者与阴性者总体生存率(overall survival,OS)的差异均有统计学意义(P＜0.05).Cox回归分析多因素显示:淋巴结转移、p53、Ki-67及E-cadherin表达是影响TNBC患者总体生存率的独立预后因素(均P＜0.05).结论:TNBC组织中,p53、Ki-67高表达,其表达阳性者预后差,E-cadherin低表达,其表达阳性者预后良好.联合检测p53、Ki-67及E-cadherin表达可为TNBC患者的治疗提供新靶点.     

Methylation-dependent silencing of CST6 in primary human breast tumors and metastatic lesions

CST6 is a breast tumor suppressor gene that is expressed in normal breast epithelium, but is epigenetically silenced as a consequence of promoter hypermethylation in metastatic breast cancer cell lines. In the current study, we investigated the expression and methylation status of CST6 in primary breast tumors and lymph node metastases. 25/45 (56%) primary tumors and 17/20 (85%) lymph node metastases expressed significantly lower levels of cystatin M compared to normal breast tissue. Bisulfite sequencing demonstrated CST6 promoter hypermethylation in 11/23 (48%) neoplastic lesions analyzed, including 3/11 (27%) primary tumors and 8/12 (67%) lymph node metastases. In most cases (12/23, 52%), the expression of cystatin M directly reflected CST6 promoter methylation status. In remaining lesions (8/23, 35%) loss of cystatin M was not associated with CST6 promoter hypermethylation, indicating that other mechanisms can account for loss of CST6 expression. These results show that methylation-dependent silencing of CST6 occurs in a subset of primary breast cancers, but more frequently in metastatic lesions, possibly reflecting progression-related genomic events. To examine this possibility, primary breast tumors and matched lymph node metastases were analyzed. In 2/3 (67%) patients, primary tumors were positive for cystatin M and negative for CST6 promoter methylation, and matched metastatic lesions lacked cystatin M expression and CST6 was hypermethylated. This observation suggests that progression-related epigenetic alterations in CST6 gene expression can accompany metastatic spread from a primary tumor site. Overall, the results of the current investigation suggest that methylation-dependent epigenetic silencing of CST6 represents an important mechanism for loss of CST6 during breast tumorigenesis and/or progression to metastasis.     

Expression of cell adhesion molecules, CD44s and E-cadherin, and microvessel density in invasive micropapillary carcinoma of the breast

AIMS: Invasive micropapillary carcinoma (IMPC) is a rare variant of ductal carcinoma of the breast and is characterized by high metastatic potential and an aggressive clinical course. This tumour is hence ideal for studying the mechanism underlying tumour biological behaviour, especially metastasis. Cell adhesion molecules, such as CD44 and E-cadherin (Ecad), and angiogenesis are considered important in the invasion and metastasis of tumours. METHODS AND RESULTS: We immunohistochemically analysed 23 IMPCs for expression of a standard form of CD44 (CD44s), Ecad, and CD34 to measure microvessel density (MVD). Results are compared with the changes observed in 23 tubular carcinomas (TCs), another variant of ductal carcinoma that rarely metastasizes. Evaluation of haematoxylin and eosin (H&E) sections showed a higher prevalence of lymph-vascular invasion (19/23, 83%) and regional lymph node involvement (12/15, 80%) in IMPCs; whereas no lymph-vascular invasion or lymph node metastasis was identified in TCs. Loss or reduction of CD44s immunoreactivity was significantly frequent in IMPC (39%) compared with TC (4%) (P = 0.0098), and was associated with positive axillary lymph nodes and lymph-vascular invasion. All cases of IMPC and TC strongly expressed Ecad. MVD (in five 200x fields) was significantly higher in IMPC (88 +/- 37) than in TC (57 +/- 16) (P = 0.001). In the IMPC group, MDV was higher in cases with positive lymph node(s) (P = 0.048), and cases with loss or reduction of CD44s expression (P = 0.011). The same trend was also demonstrated in cases with lymph-vascular invasion (P = 0.077). Moreover, the vessels in IMPC had much smaller calibres with thinner walls than those in TC. CONCLUSIONS: Loss of the CD44 adhesion molecule and high MVD may play a significant role in the high incidence of lymph-vascular permeation and metastasis in IMPC.     

Prognostic significance of Ki-67, p53, and Bcl-2 expression in prostate cancer patients with lymph node metastases: A retrospective immunohistochemical analysis

The prognostic significance of Ki-67, p53, and Bcl-2 expression was evaluated in prostate cancer patients with lymph node metastases. Immunohistochemical staining of archived material obtained from 56 patients was performed by the streptavldin-biotin method. Univariate survival analysis showed that a Ki-67 labeling index (Ki-67 LI) of ≥8.4 in the primary tumor identified a group of patients with a significantly poorer prognosis (P<0.001). Furthermore, a Ki-67 LI of ≥8.7 in the nodal metastatlc tumor was also associated with a poorer prognosis (P<0.01). Multivariate analysis showed that the Ki-67 LI of primary tumors (P<0.01) and lymph node metastases (P<0.01) had independent prognostic value. p53 and Bcl-2 expression had no prognostic value in patients with prostate cancer and lymph node involvement. The Ki-67 LI has more prognostic value than p53 and Bcl-2 expression for patients with prostate cancer that has spread to the lymph nodes.     

肿瘤转移抑制基因nm23—H1 mRNA在乳腺癌中的转录表达

目的：探讨nm23—H1基因mRNA在乳腺患组织中的表达及其与临床的关系．方法:采用半定量RT—PCR方法，检测30例乳腺患组织nm23—H1的表达．结果:①淋巴结阳性的原发灶组织nm23—H1 mRNAA表达明显低于淋巴结阴性的原发灶组织，Ⅲ期乳腺患组织nm23—H1 mRNA水平较Ⅰ、Ⅱ期的明显低．②多因素分析发现淋巴结转移与nm23—H1 mRNA的表达有显著性相关．结论nm23—H1基因mRNA表达强度与淋巴结转移呈负相关．在乳胰患转移过程中，nm23—H1 mRNA起重要的作用。     

The c-erbB-2 Protein in Primary and Metastatic Breast Carcinomas

Material from 41 patients with primary breast carcinoma and lymph node metastases at the time of primary surgical intervention was immunostained for c-erbB-2 protein, neuron-specific enolase (NSE), and estrogen receptors. Thirty of the primary breast carcinomas were of ductal type. Six were classified as infiltrating lobular carcinomas, 2 were apocrine, 1 was mucinous, and 1 was a tubular carcinoma. One tumor could not be classified as ductal or lobular by light microscopic examination alone. The number of lymph node metastases available varied from 1 to 14 per case (median, 3.9). Nine (22%) of the primary breast carcinomas (8 ductal and 1 apocrine) expressed c-erbB-2 protein and showed c-erbB-2 gene amplification; 12 expressed NSE immunoreactivity. None expressed both markers. Estrogen receptor immunoreactivity was present in 23 of the 41 cases, including 9 of the NSE-positive cases. C-erbB-2 protein-positive metastases were present in 18 cases (44%), and in 13 cases all metastases were immunostained. In 5 cases the expression of c-erbB-2 protein varied from metastasis to metastasis. NSE immunoreactivity was expressed in 10 cases, and in 3 cases with minor NSE-positive cell populations the metastatic lesions expressed c-erbB-2 protein as well. All 9 primary breast carcinomas expressing c-erbB-2 protein had lymph node metastases with c-erbB-2-immunoreactive tumor cells. Eight of the 9 c-erbB-2 protein-negative primary tumors with metastases expressing c-erbB-2 protein showed no amplification of the c-erbB-2 gene. Thus expression of c-erbB-2 protein can occur during the metastatic process, even if it seems to be missing in the primary tumor. On the other hand, if a primary breast carcinoma expresses c-erbB-2 protein, this feature seems to be present in all the tumor metastases as well.     

浸润性乳腺癌及转移淋巴结中RKIP和Ki-67的表达及意义

目的 探讨RKIP和Ki-67在浸润性乳腺癌及其淋巴结转移灶中的表达及意义.方法 应用免疫组化SP法检测RKIP和Ki-67在52例浸润性乳腺癌及其淋巴结转移灶中的表达情况.结果 乳腺癌淋巴结转移灶与原发灶相比,RKIP表达水平明显下降,两者之间有统计学差异(P<0.01).Ki-67指数在乳腺癌淋巴结转移灶明显高于原发灶(P<0.01);但RKIP与Ki-67之间,无论是原发灶,还是转移灶,都无相关关系(均P>0.05).结论 RKIP具有抑制浸润性乳腺癌转移的作用,属于转移抑制基因;Ki-67可反映乳腺癌的增殖活性及转移和预后,但RKIP的表达对乳腺癌细胞的增殖无明显影响.     

Immunohistochemical expression of gonadotropin releasing hormone receptor in human breast carcinoma

Gonadotropin releasing hormone (GnRH) analogs can cause regression of hormone-dependent breast carcinomas via the specific GnRH receptor (GnRH-R). In an attempt to obtain a better understanding of GnRH actions in human breast carcinoma, the expression of GnRH-R was examined immunohistochemically in 58 invasive ductal carcinomas and correlated with various clinicopathological parameters. GnRH-R was immunolocalized in the cytoplasm of carcinoma cells in 37 of 58 invasive ductal carcinoma cases (64%). Immunoreactivity for GnRH-R was also detected focally in the cytoplasm of morphologically normal glandular epithelia adjacent to the carcinoma. A significant correlation was observed between the immunohistochemical expression of GnRH-R and estrogen receptor labeling index (LI; P = 0.030) or progesterone receptor LI (P = 0.0074). There was a significant inverse correlation between GnRH-R immunoreactivity and Ki-67 LI (P = 0.012). No significant correlations were detected between GnRH-R and other clinicopathological parameters, including patient age, menopausal status, stage, tumor size, lymph node status, histological grade and prognosis. This study indicates that GnRH-R is widely distributed in human breast carcinoma cells and regulates GnRH actions locally. Breast carcinomas positive for GnRH-R maintain some hormonal regulatory mechanisms, and GnRH actions may lead to a low proliferative rate in human breast carcinoma.     

The Quarterly Case: Metastatic Tumor of Unknown Origin

Material from 41 patients with primary breast carcinoma and lymph node metastases at the time of primary surgical intervention was immunostained for c-erbB-2 protein, neuron-specific enolase (NSE), and estrogen receptors. Thirty of the primary breast carcinomas were of ductal type. Six were classified as infiltrating lobular carcinomas, 2 were apocrine, 1 was mucinous, and 1 was a tubular carcinoma. One tumor could not be classified as ductal or lobular by light microscopic examination alone. The number of lymph node metastases available varied from 1 to 14 per case (median, 3.9). Nine (22%) of the primary breast carcinomas (8 ductal and 1 apocrine) expressed c-erbB-2 protein and showed c-erbB-2 gene amplification; 12 expressed NSE immunoreactivity. None expressed both markers. Estrogen receptor immunoreactivity was present in 23 of the 41 cases, including 9 of the NSE-positive cases. C-erbB-2 protein-positive metastases were present in 18 cases (44%), and in 13 cases all metastases were immunostained. In 5 cases the expression of c-erbB-2 protein varied from metastasis to metastasis. NSE immunoreactivity was expressed in 10 cases, and in 3 cases with minor NSE-positive cell populations the metastatic lesions expressed c-erbB-2 protein as well. All 9 primary breast carcinomas expressing c-erbB-2 protein had lymph node metastases with c-erbB-2-immunoreactive tumor cells. Eight of the 9 c-erbB-2 protein-negative primary tumors with metastases expressing c-erbB-2 protein showed no amplification of the c-erbB-2 gene. Thus expression of c-erbB-2 protein can occur during the metastatic process, even if it seems to be missing in the primary tumor. On the other hand, if a primary breast carcinoma expresses c-erbB-2 protein, this feature seems to be present in all the tumor metastases as well.     

埃兹蛋白在乳腺癌中的表达及其临床意义

目的 通过检测埃兹蛋白在浸润性乳腺癌、乳腺导管内癌及正常乳腺组织中的表达,探究埃兹蛋白在乳腺癌组织中的表达的临床意义。方法 随机选取南昌大学第一附属医院40例浸润性乳腺癌患者及32例乳腺导管内癌患者,另外选择同期来我院健康体检者22例。通过免疫组化链霉亲和素-过氧化物酶法（S-P）法分别检测埃兹蛋白在22例正常乳腺组织、32例乳腺导管内癌组织和40例浸润性乳腺癌组织中的表达,参照病理结果进行分析。结果 埃兹蛋白在40例浸润性乳腺癌的阳性表达率为72.50%、在32例乳腺导管内癌的阳性表达率为40.63%、在正常乳腺组织中的阳性表达率13.64%,浸润性乳腺癌中埃兹蛋白的表达高于其他两种组织,差异具有统计学意义（P＜0.05）;埃兹蛋白在G3期乳腺癌组织中的表达高于在G1~G2期乳腺癌组织中的表达,差异具有统计学意义（P＜0.05）;埃兹蛋白在淋巴结转移患者中的阳性表达率高于在无淋巴结转移的患者中的阳性表达率,差异统计学意义显著（P＜0.01）;埃兹蛋白在＜40岁的患者中的阳性表达率低于在年龄≥40岁的患者中的表达率,差异统计学意义显著（P＜0.01）;埃兹蛋白在PR阳性患者中的阳性表达率低于在PR阴性患者中的表达率,差异具有统计学意义（P＜0.05）;乳腺癌患者中埃兹蛋白的表达与组织学分级、腋窝淋巴结转移及年龄呈正相关（P＜0.05）,与PR呈负相关（P＜0.05）;埃兹蛋白在浸润性润腺癌中的表达与乳腺癌临床分期、脉管侵犯、肿瘤大小、患者月经状态以及Her-2、ER、Ki-67的表达无相关性（P＞0.05）。结论 埃兹蛋白在乳腺癌和正常乳腺组织中的表达不同,对判断乳腺肿瘤性质具有重要参考意义;此外,埃兹蛋白能够帮助判断乳腺癌的转移潜能和预后,可能启发乳腺癌新的靶向治疗。     

层粘连蛋白受体和nm23蛋白在乳腺癌组织中的表达及其与间 …

探讨乳腺癌组织层粘连蛋白（ＬＮ）及其受体（ＬＮ－Ｒ）和ｎｍ２３蛋白的表达与间质微血管密度及肿瘤转移的关系。方法应用免疫组织化学ＬＳＡＢ方法检测７３例乳腺癌力ｎｍ２３蛋白的表达,在第Ⅷ因子相关抗原染色切片上检测其微血管密度（ＭＶＤ）。结果病理分级越高,乳腺癌ＬＮ表达程度越强,即病理Ⅰ级而ＬＮ分布Ⅲ级者为８．３％,病理和ＬＮ分布均Ⅲ级者为５８．８％,两者间差异有极显著意义。ＬＮ－Ｒ表达程度则与转移有关     

DEK overexpression is correlated with the clinical features of breast cancer

To investigate the clinicopathological significance of DEK overexpression in breast cancers, a total of 196 cases, including 20 of normal tissues, 12 of intraductal hyperplasia, 31 of ductal carcinoma in situ (DCIS) and 133 of invasive ductal carcinoma of the breast, were selected from the Department of Pathology, Yanbian Tumor Hospital for immunohistochemical staining of DEK, estrogen (ER), progesterone (PR) and Ki-67 proteins. In results, DEK protein had higher positivity in DCIS, compared with the adjacent normal breast tissues. Also, DEK protein was strongly positive in invasive ductal carcinoma of the breast on immunohistochemistry, which was significantly higher than normal breast tissues. However, only two (2/12) cases of intraductal hyperplasia of the breast showed positive staining for DEK protein. Additionally, DEK overexpression was significantly correlated with the increased proliferating index of Ki-67. For the histological grade, DEK positive rate was only 39.6% in G1 breast cancers, but significantly higher in G2 (92.3%) and G3 (97.0%) cases (P<0.05). Also, a strongly positive rate of DEK was lower in Stage-0 (21.4%) and Stage-I (40.9%) compared with Stage-IIa (87.5%), Stage-IIb (89.7%) and Stage-IIIa (92.3%) (P<0.05). And DEK protein showed higher expression level in < 3 years disease free survival breast cancers than it did in ≥ 3 years disease free survival cases (P<0.05). However, no statistically difference was found among DEK expression, lymph node metastasis, and ER and PR expressions. In conclusion, DEK overexpression appears to be associated with breast cancer progression and DEK may potentially be used as a breast cancer biomarker for the early diagnosis, prognostic evaluation and therapeutic target for breast cancer.     

Organotropism and prognostic marker discordance in distant metastases of breast carcinoma: fact or fiction? A clinicopathologic analysis

Prior studies have suggested that the type of breast cancer influences the location of distant metastases ("organotropism") and that there may be discordance of estrogen receptor and human epidermal growth factor receptor 2 (Her2) expression between primaries and metastases. Our aims were to investigate the relationship between tumor type and metastatic site and to compare biomarker expression between primary and metastatic tumors. We retrospectively reviewed 102 biopsy-proven cases of breast cancer metastatic to distant sites from 2000 to 2010 and 34 corresponding primaries for histologic subtype, grade, lymphovascular invasion, lymph node metastasis, and expression of estrogen receptor and Her2. Most metastases were of ductal (88) and lobular (11) histologic types. Available data on primaries indicated that the majority were grade III with positive lymph node metastasis and lymphovascular invasion. Biomarkers on 73 metastases showed 37 estrogen receptor positive/Her2-, 6 estrogen receptor positive/Her2+, 8 estrogen receptor negative/Her2+, and 22 estrogen receptor negative/Her2-. The most common metastatic sites were the lung (26%), bone (32%), and liver (21%). We found no association between estrogen receptor/Her2 profile and metastatic site (P = .16). When compared with ductal carcinoma, lobular carcinoma showed a unique metastatic pattern to gastrointestinal tract/gynecologic sites (P = .014). Of 34 cases with paired prognostic markers for primary and metastatic sites, 7 (20%) demonstrated discordance in estrogen receptor-positive/Her2 profile between the primary and the metastasis. Because the estrogen receptor-positive/Her2 profile of metastatic breast cancer did not always match that of the primary tumor, it is important to repeat the prognostic markers of metastasis.     

Comparison of proliferative activities and metastases between two subtypes classified at the deeply infiltrating sites of colorectal moderately differentiated adenocarcinomas

Twenty-eight moderately differentiated adenocarcinomas invading beyond the muscularis propria of the colorectum were subclassified as 13 moderate- and 15 poor-subtype tumors based on the histology at the deeply infiltrating sites. Moderately differentiated cancer cells were correlated with liver metastasis and p53 immunoreactivity. Poorly differentiated cancer cells were correlated with lymph node metastases but not to p53 immunoreactivity. The proliferative cell nuclear antigen (PCNA) labeling index (LI), Ki-67 LI and agyrophilic nuclear organizer regions (AgNOR) values determined for the poorly differentiated cancer cells in the poor-subtype tumors were significantly lower than those of moderately differentiated cancer cells in the moderate-subtype tumors. In cells from tumors classified as poor-subtype, poor differentiation was associated with decreased PCNA LI levels, but with unchanged Ki-67 LI and AgNOR values. These results indicate that colorectal adenocarcinoma cells that are histologically subclassified as moderately differentiated have different proliferative and metastatic activities from cancer cells that are poorly differentiated. Moderately differentiated cancer cells are associated with hematogenous metastasis to liver and high proliferative activity, and loss of tubular formation of cancer cells may be fundamentally related to lymph node metastasis and infiltrative growth.     

Expression of p53 and NDP-K/nm23 in gastric carcinomas--association with metastasis and clinicopathologic parameters.

To evaluate the role of p53 and NDP-K/nm23(nm23) protein as a prognostic factor and their relation to metastasis of cancer, we studied metastatic and nonmetastatic gastric carcinoma specimens by immunohistochemical staining. Among the 101 specimens examined, 37(36.6%) showed positivity in staining for p53 protein and 64(63.4%) showed no detectable p53 protein in tumor cells. p53 overexpression was correlated with depth of invasion, lymphatic invasion, lymph node metastasis and distant metastasis. Out of 101 specimens, 35 cases had no staining for nm23. 62 cases(61.4%) exhibited a cytoplasmic staining on most cells and 42 cases (41.6%) had nuclear staining. In 16 of 101 cases(15.8%), a mild to moderate membranous staining was observed in some cells. Cytoplasmic nm23 expression was negatively correlated with lymph node metastasis(P < 0.01) and distant metastasis(P < 0.01). The nuclear nm23 expression showed negative correlation with depth of invasion(P < 0.01), lymphatic invasion(P < 0.01), lymph node metastasis(P < 0.01), and distant metastasis(P < 0.04). The membranous nm23 expression revealed negative correlation with lymphatic invasion(P < 0.02), lymph node metastasis(P < 0.01) and distant metastasis(P < 0.02).     

Inactivation of the PTEN gene protein product is associated with the invasiveness and metastasis, but not angiogenesis, of breast cancer

PTEN is a novel tumor-suppressor gene located on chromosomal band 10q23. Loss of PTEN function has been implicated in the progression of several types of cancer, but the correlation between loss of PTEN expression and advanced carcinomas is not well established. The capacity for angiogenesis of a tumor is known to play a very important role in growth and metastasis, and there have been reports that PTEN relates to angiogenesis. In the present study, formalin-fixed and paraffin embedded tissues from 101 patients with breast carcinomas, including 88 cases of invasive ductal carcinomas and 13 cases of ductal carcinoma in situ (DCIS), were evaluated by immunohistochemical methods for the expression of PTEN and vascular endothelial growth factor (VEGF), as well as microvessel density (MVD). The results were compared with the clinicopathologic parameters. There was no loss of PTEN expression in any of the cases of DCIS, but 28 (32%) of the 88 invasive cases did not express PTEN. Loss of PTEN expression was associated with lymph node metastasis ( P  = 0.03), but did not correlate with tumor size, tumor grade, MVD or recurrence. VEGF expression significantly correlated with lymph node metastasis in invasive ductal carcinoma ( P  = 0.01). There was no correlation between the expression of PTEN and that of VEGF ( P  = 0.63). The present study suggests that loss of PTEN expression is common and correlates with tumor progression and lymph node metastasis in breast carcinoma. The relationship between loss of PTEN and progression of breast cancer may not be explained by modulation of angiogenesis.