MDR、C-erbB-2和ER、PR在乳腺癌中的表达

目的 探讨乳腺癌中多药耐药基因产物P170糖蛋白、癌基因c-erbB-2和雌激素受体(ER)、孕激素受体(PR)的表达情况及临床意义。方法采用S-P免疫组化方法对40例乳腺癌组织进行P170、C-erbB-2和ER、．PR表达的联合检测。结果乳腺癌组织中P170、c-erbB一2和ER、PR阳性表达率分别为32．5％、35%、62．5％、30％。P170的表达与术前化疗史及腋窝淋巴结转移呈正相关，与ER、PR的表达无显著相关性。C-erbB-2表达与与腋窝淋巴结转移呈正相关，与ER、PR的表达呈负相关。ER的表达与组织学分级和腋窝淋巴结转移呈负相关，随着年龄增大表达率有升高趋势。结论P170、C-erbB-2和ER、PR与乳腺癌的发生发展有关。耐药基因P170的检测有利于指导乳腺癌的化疗和判断预后。C-erbB-2可作为判断乳腺癌预后的重要指标。ER、PR测定可判断预后，有利于选择乳腺癌内分泌治疗。     

胃癌的雌孕激素受体状况与预后关系的临床探讨

目的探讨胃癌的雌、孕激素受体状况与预后关系。方法对３４例胃癌根治术后的标本以免疫组化（ＡＢＣ法）作ＥＲ、ＰＲ测定,并作５ａ随访。结果ＥＲ、ＰＲ阳性率皆为４１．２％（１４／３４）。高分化胃癌ＥＲ、ＰＲ阳性率（２６．９％）明显低于分化差的胃癌组（８７．５％）。随访５ａ,存活者中原来标记的ＥＲ、ＰＲ阳性率较低,仅为２０％。结论胃癌根治术后除辅以化疗外,ＥＲ、ＰＲ阳性者加内分泌治疗可能会提高５ａ生存率。     

雌、肝激素受体检测与食管癌的临床病理研究

目的 研究食管癌雌、孕激素受体与食管癌预后的关系。方法 用免疫组化法（改良PAP法）对61例食管癌组织检测ER（雌激素受体）、PR（孕激素受体。结果（1）ER或PR阳性食管癌术后生存期高于ER或PR阴性者（P<0.01)。ER或PR阳性的女性术后生存期高于ER或PR阳性的男性术后生存期，ER或PR阳性的男性术后生存期高于ER或PR阴性的男性术后生存期；（2）ER、PR的表达与仞管癌的分化程度有关，人退休费程度越高，ER、PR阳性率越高；（3）ER、PR表达与食管癌患者的年龄、性别、临床分期、淋巴结转移及肿瘤大小无明显关系。结论 雌、孕激素受体阳性的食管癌细胞能被雌激素抑制生长，雌、孕激素受体阳性的食管癌术后生存期长。     

66例乳腺癌的临床与病理分析

目的探讨乳腺癌的病理类型与淋巴结转移及ER、PR表达的关系。方法回顾性分析66例乳腺癌的临床病理资料。结果浸润性导管癌24例、单纯癌30例，其余12例为其他较少见的病理类型。发病平均年龄51岁，41-50岁为高峰期；单纯癌和浸润导管癌两种病理类型的淋巴结转移率和ER、PR阳性率差异无统计学差异（P〉0．05）。结论乳腺癌的发病趋向年轻化，不同病理类型与淋巴结转移率和ER、PR阳性率没有相关性。     

乳腺癌雌、孕激素受体与腋淋巴结转移的关系

目的探讨乳腺癌雌、孕激素受体(ER、PR)与淋巴结转移之间的关系.方法应用免疫组织化学方法对257例乳腺癌组织石蜡切片进行ER、PR检测,将ER、PR结果与病理检出淋巴结的结果进行统计学分析.结果 ER、PR的阳性表达率分别为63.27%和59.27%.在ER、PR的4种组合中淋巴结转移率基本相同,经统计学处理均无显著差异(P＞0.05).结论乳腺癌组织中的ER、PR阳性表达与淋巴结转移无关.ER、PR测定对指导内分泌治疗和估计预后有重要意义.     

青年乳腺癌病理特点-附60例病例分析

目的探讨35岁以下青年乳腺癌临床病理特点。方法回顾性分析60例青年乳腺癌病例的临床特点、肿瘤大小、病例分级、淋巴结转移、TNM分期及部分病例雌、孕激素受体(ER、PR)蛋白表达情况。并随机抽取同期非青年乳腺癌60例作为对照进行比较。结果青年乳腺癌以浸润性导管癌为主(49例,占81%),其次为浸润性小叶癌(17例,占28%)。腋下淋巴结转移阳性者42例,占总数的70%,明显高于对照组(P=0.006)。C-erbB2及VEGF蛋白表达水平高于对照组,ER、PR水平低于对照组(P<0.05);两组临床分期无统计学差异(P>0.05)。结论35岁以下青年乳腺癌在病理学特征上表现独特。且误诊率高,进展快,转移早,提示预后差。早期诊断是提高其生存率的唯一有效手段。     

肥胖与乳腺癌临床生物学特性

本文应用身体指数[体重(公斤)/身高(米)~2]分析肥胖对乳腺癌临床生物学特性的影响。740例女性乳腺癌病人,按身体指数大小分成消瘦组(≤21.0)、普通组(21.1～23.0)和肥胖组(>23.0)。结果表明,乳房肿块大,淋巴结转移度高者均以肥胖组居多,有统计学意义(p<0.05,p<0.001);而雌激素受体状态与胖瘦无关。我们认为,肥胖对乳腺癌的预后有影响。     

56例隐匿性乳腺癌临床病理特征分析及诊疗策略探讨

背景与目的：隐匿性乳腺癌发病隐匿,诊断困难,治疗策略不确定,是乳腺癌领域的难点和热点。本研究探讨了隐匿性乳腺癌的临床病理特征及诊疗策略。方法：对56例隐匿性乳腺癌患者在术前采用乳腺彩超、钼靶、磁共振及PET/CT检查,对比不同检查方法对隐匿性乳腺癌可疑原发灶检出率及病理符合率的差异。治疗方案采用新辅助化疗、乳腺癌改良根治术、保乳+腋窝淋巴结清扫术、腋窝淋巴结清扫术,术后行化疗+放疗。结果：乳腺超声、X线、MRI、PET/CT对乳腺可疑原发灶的检出率分别为7.14%（4/56）、29.41%（15/51）、37.50%（18/48）和16.28%（7/43）;结合术后病理学检查发现其病理符合率分别为66.67%（2/3）、50.00%（7/14）、50.00%（9/18）和50.00%（3/6）;26例患者乳腺超声、X线及MRI均未发现可疑原发灶,其中21例接受病理学检查,阳性率为14.29%（3/21）;对39例乳腺癌改良根治术标本行乳腺病理切片检查,检出原发灶15例,检出率38.46%。根据St. Gallen指南分子分型标准,Luminal A型、Luminal B型、HER-2阳性型和三阴性型比例分别为7.14%、46.43%、12.50%和33.93%。术后随访52例,随访时间10~104个月,中位时间35个月,复发转移4例,死亡0例。检出原发灶的15例患者中,复发或转移2例;未检出原发灶的24例患者中,无复发或转移;行新辅助化疗17例,达病理学完全缓解（pathological complete response,PCR）2例,复发或转移2例;行乳腺癌改良根治术39例,复发或转移2例;行保乳+腋窝清扫8例,复发或转移2例;腋窝清扫9例,无复发或转移。结论：乳腺MRI检查在隐匿性乳腺癌的排除性诊断中有重要价值;乳腺超声、X线及MRI均未发现可疑原发灶的患者其乳腺病理原发灶检出率较低;隐匿性乳腺癌的治疗策略可选择新辅助化疗、乳腺癌改良根治术、保乳+腋窝清扫术、腋窝清扫术;乳腺病理学未检出原发灶的患者复发转移率低于检出原发灶者。     

乳腺癌伴同侧锁骨上淋巴结转移的治疗

乳腺癌伴同侧锁骨上淋巴结转移(breast cancer with ipsilateral supraclavicular lymph node metastasis,ISLM)的分期曾一度改变.在1988年第5版的AJCC分期中,同侧锁骨上淋巴结的转移被定义为真正的远处转移,然而在2003年AJCC和UICC乳腺癌分期指南中规定,如果不伴有其他远处转移,同侧锁骨上淋巴结的转移划分为pN3c,被认为是局部晚期病变.虽然乳腺癌伴同侧锁骨上淋巴结转移患者预后明显好于真正M1患者,但其最佳治疗手段一直是探讨的热点,本文查阅相关文献,对乳腺癌伴同侧锁骨上淋巴结转移的治疗进展进行了简要综述.     

Altered local and systemic immune profiles underlie lymph node metastasis in breast cancer patients

Cancer‐mediated immune dysfunction contributes to tumor progression and correlates with patient outcome. Metastasis to tumor draining lymph nodes (TDLNs) is an important step in breast cancer progression and is used to predict patient outcome and survival. Although lymph nodes are important immune organs, the role of immune cells in TDLNs has not been thoroughly investigated. We hypothesized that the host immune response in node negative (NN) patients is more intact and thereby can resist tumor invasion compared to node positive (NP) patients. As such, lymph node metastasis requires breakdown of the host immune response in addition to escape of cancer cells from the tumor. To investigate the immunological differences between NN and NP breast cancer patients, we purified and profiled immune cells from the three major compartments where cancer and immune cells interact: tumor, TDLNs and peripheral blood. Significant down‐regulation of genes associated with immune‐related pathways and up‐regulation of genes associated with tumor‐promoting pathways was consistently observed in NP patients' TDLNs compared to NN patients. Importantly, these signatures were seen even in NP patients' tumor‐free TDLNs, suggesting that such immune changes are not driven solely by local tumor invasion. Furthermore, similar patterns were also observed in NP patients' tumor and blood immune cells, suggesting that immunological differences between NN and NP patients are systemic. Together, these findings suggest that alterations in overall immune function may underlie risk for LN metastasis in breast cancer patients.     

RAGE和HMGB1在乳腺癌中表达及其临床意义

目的探讨乳腺癌组织中RAGE和HMGB1基因表达及其临床意义。方法各对50例早期、晚期乳腺癌组织及正常乳腺组织蜡块标本,运用real-time PCR技术检测RAGE和HMGB1基因的表达情况。并分析各基因表达与乳腺癌组织的分化程度、浸润深度、淋巴结转移、TNM分期之间的关系。结果 RAGE和HMGB1基因表达荧光实时定量PCR法上调分别为73%、79%。乳腺癌TNM分期、淋巴结转移与基因高表达有密切关系,RAGE基因表达与HMGB1表达呈正相关(P<0.05)。结论 RAGE和HMGB1基因表达对于乳腺癌早期诊断和预后分析有重要指导意义,根据其表达开展有选择性地基因治疗应有良好的应用前景。     

乳腺癌组织内VEGFR-3的表达与淋巴结转移的关系

目的:检测乳腺癌组织内血管内皮生长因子受体-3(VEGFR-3)的表达和淋巴管密度(LVD)及淋巴结转移的相关性。方法:应用免疫组化SABC法检测45例乳腺癌组织、癌旁组织中VEGFR-3的表达并计数LVD,分析其与患者年龄、临床病理学分级、组织分化程度及淋巴结转移的相关性。结果:乳腺癌组织内VEGFR-3的表达与患者年龄、临床病理学分级、组织分化程度无关(P>0.05),而与淋巴结转移密切相关(P<0.05),癌组织、癌旁组织有淋巴结转移组的LVD均高于无淋巴结转移组,差异有显著性(P<0.05)。结论:乳腺癌组织内VEGFR-3的表达与LVD及淋巴结转移密切相关,可作为乳腺癌淋巴结转移的预测因子。     

青、老年乳腺癌淋巴结转移规律的分析

目的　探讨青、老年乳腺癌淋巴结转移规律。方法　对 1988年 5月～ 1996年 5月间收治的青、老年乳腺癌患者 118例 ,其中青年组乳腺癌 5 8例 (≤ 3 5岁 ,为A组 ) ,老年组乳腺癌 60例 (≥ 60岁 ,为B组 )。各组淋巴结逐个做石蜡切片 ,记录每组中收集淋巴结个数及转移个数并作对比分析。结果　A组的淋巴结转移率为 72 .4% (4 2 /5 8)及转移度为 3 7.8% (2 3 8/63 0 ) ,均明显高于B组的 46.7% (2 8/60 )及 2 0 .4% (13 8/678) (P <0 .0 1)。肿瘤大小、浸润深度、病理分类、组织分级、ER等在相同条件下比较 ,淋巴结转移率均以A组高 (P <0 .0 5 )。结论　青年乳腺癌具有更强的侵袭性 ,易发生淋巴结转移。     

Angiogenesis and hypoxia in lymph node metastases is predicted by the angiogenesis and hypoxia in the primary tumour in patients with breast cancer

Hypoxia and angiogenesis are important factors in breast cancer progression. Little is known of hypoxia and angiogenesis in lymph node metastases of breast cancer. The aim of this study was to quantify hypoxia, by hypoxia-induced marker expression levels, and angiogenesis, by endothelial cell proliferation, comparing primary breast tumours and axillary lymph node metastases. Tissue sections of the primary tumour and a lymph node metastasis of 60 patients with breast cancer were immunohistochemically stained for the hypoxia-markers carbonic anhydrase 9 (CA9), hypoxia-inducible factor-1alpha (Hif-1alpha) and DEC-1 and for CD34/Ki-67. Endothelial cell proliferation fraction (ECP%) and tumour cell proliferation fraction (TCP%) were assessed. On haematoxylin-eosin stain, the growth pattern and the presence of a fibrotic focus were assessed. Hypoxia-marker expression, ECP% and TCP% in primary tumours and in lymph node metastases were correlated to each other and to clinico-pathological variables. Median ECP% and TCP% in primary tumours and lymph node metastases were comparable (primary tumours: ECP%=4.02, TCP%=19.54; lymph node metastases: ECP%=5.47, TCP%=21.26). ECP% correlated with TCP% (primary tumours: r=0.63, P<0.001; lymph node metastases: r=0.76, P<0.001). CA9 and Hif-1alpha expression were correlated (primary tumours P=0.005; lymph node metastases P<0.001). In primary tumours, CA9 and Hif-1alpha expression were correlated with DEC-1 expression (P=0.05), presence of a fibrotic focus (P<0.007) and mixed/expansive growth pattern (P<0.001). Primary tumours and lymph node metastases with CA9 or Hif-1alpha expression had a higher ECP% and TCP% (P<0.003); in primary tumours, mixed/expansive growth pattern and fibrotic focus were characterised by higher ECP% (P=0.03). Furthermore, between primary tumours and lymph node metastases a correlation was found for ECP%, TCP%, CA9 and Hif-1alpha expression (ECP% r=0.51, P<0.001; TCP r=0.77, P<0.001; CA9 and Hif-1alpha P<0.001). Our data demonstrate that the growth of breast cancer lymph node metastases is angiogenesis dependent and that angiogenesis and hypoxia in the primary tumour predict angiogenesis and hypoxia in the lymph node metastases. Together with previous findings in breast cancer liver metastases, which grow in 96% of cases angiogenesis independently, these data suggest that both the intrinsic growth characteristics and angiogenic potential of breast cancer cells and the site-specific tumour microenvironment determine angiogenesis and hypoxia in breast cancer.     

High PD-L1 expression was associated with poor prognosis in 870 Chinese patients with breast cancer

Background

To investigate the role of PD-L1 expression in tumor recurrence and metastasis in Chinese patients with breast cancer.

Methods

Suitable tissue samples were available from 870 patients with breast cancer. Paraffin-embedded tumor sections were stained with PD-L1 antibody. The correlations between PD-L1 expression and clinical characteristics, ER/PR/HER2 status and survival parameters were analyzed. Kaplan-Meier and univariate Cox proportional hazards model analyses were used to compare the survival of patients with high PD-L1 expression and patients with no PD-L1 expression.

Results

The median follow-up time was 98 months(range, 17–265 months). The positive rate of PD-L1 expression in breast cancer was 21.7% (189/870). PD-L1 high expression was inversely associated with larger tumor size, higher tumor grade, more positive lymph node number, as well as negative ER and PR status. PD-L1 expression was particularly higher in TNBC compared with non-TNBC, although no statistical significance was observed. Nomogram logistic regression results based on clinical and pathological features showed that the following factors were more likely associated with high PD-L1 expression: patient age younger than 35 years, larger tumor size, lymphovascular invasion and advanced stage. Our data indicated that patients with high PD-L1 expression had poor DFS, DMFS and overall survival compared with those with no PD-L1 expression. Univariate Cox proportional hazards model analysis showed that PD-L1 was an independent prognostic factor for tumor prognosis.

Conclusions

PD-L1 expression is an important indicator of unfavorable prognosis in breast cancer patients.     

2108例T1~2期乳腺癌患者腋窝淋巴结转移的相关因素分析

目的：探讨T1~2期乳腺癌患者临床与病理因素与腋窝淋巴结转移的关系,指导前哨淋巴结活检术（SL-NB）的应用,以避免腋窝清扫术（ALND）后并发症的发生。方法收集接受手术且经病理确诊的T1~2期乳腺癌病例,对其临床病理资料进行回顾性统计分析。通过单因素分析和多因素Logistic回归分析寻找乳腺癌发生腋窝淋巴结转移的影响因素。结果共2108例患者入组,其中1021例患者发生淋巴结转移（48.4%）。单因素分析显示年龄、肿瘤大小、病理类型、组织学分级、脉管瘤栓、ER、PR、Ki-67指数以及分子分型等因素与淋巴结转移有关（P﹤0.05）;而HER-2是否过表达与淋巴结转移无关。多因素Logistic回归分析显示,患者的腋窝淋巴结转移的独立影响因素为肿瘤大小、病理类型、组织学分级、脉管瘤栓、ER表达状况（P﹤0.05）;而年龄也可能是腋窝淋巴结有无转移的独立影响因素（P=0.053）。结论肿瘤越大、分化越差、伴脉管瘤栓、ER阳性表达以及病理类型为浸润性小叶癌的T1~2期乳腺癌患者的淋巴结转移风险更高,而年龄≤50岁也可能增加了腋窝淋巴结转移的风险。T1~2期乳腺癌患者是否直接行ALND应持谨慎的态度。