新辅助化疗对乳腺癌生物学指标表达的影响

目的 探讨新辅助化疗对评估原发性乳腺癌空心针穿刺活检（CNB）和手术切除标本（SES）生物学指标的影响.方法 152 例原发性乳腺癌患者纳入本研究.其中化疗组99 例,手术组53 例.采用免疫组织化学（IHC）方法 比较152 例CNB 和SES 采样组织标本中雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子2（Her2）、Ki67、p53 和TopoⅡ的表达,评估CNB 在乳腺癌生物学指标检测中的准确性.结果 CNB 和SES 在评估是否接受过新辅助化疗乳腺癌生物学指标方面具有良好的一致性,K 值〉 0.6.手术组CNB 对生物学指标评估的准确性达到87% ~ 91%,化疗组的准确性78% ~ 95%.但新辅助化疗对ER、PR、Her2、p53 和Ki67 表达的影响差异无统计学意义（P 〉 0.05）,两组间比较TopoⅡ表达差异有统计学意义（P 〈 0.05）.结论 CNB 和SES 在评估乳腺癌生物学指标上的一致性较好,CNB 评估乳腺癌生物学指标的准确性高.新辅助化疗对乳腺癌生物学指标的影响较小.     

激素受体表达在乳腺癌空芯针穿刺与手术切除标本符合率的研究

目的 :探讨雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)和Her-2在乳腺癌空芯针穿刺(core needle biopsy,CNB)标本与手术切除标本的表达和符合率。方法:本研究为我院接受乳腺癌手术治疗、术前行CNB检测的病人,对配对的CNB和手术切除标本进行ER、PR和Her-2表达的检测,比较其结果和符合率。结果:136例乳腺癌病人ER、PR和Her-2的阳性率分别为78.7%、61.8%和22.1%,与手术切除标本的77.9%、64.7%和20.6%相比较,无统计学差异(P>0.05)。ER、PR和Her-2在CNB与手术切除标本的符合率分别为96.3%、86.8%和98.5%,κ值均>0.6(P     

乳腺癌术前核芯针穿刺检测ER、PR、C-erbB-2、Ki-67的临床研究

目的：探讨术前核芯针穿刺活检（CNB）免疫组织化学检测ER、PR、C-erbB-2、Ki-67在乳腺癌诊断中的临床应用价值。方法：35例乳腺癌患者术中局部切除肿瘤后,送快速病理前,在手术室中采用巴德枪对肿瘤进行核芯针穿刺取材,模拟术前乳腺癌CNB,取得病理组织学及免疫组织化学检测结果后,与术后病理及免疫组织化学检查结果进行对比。结果：35例乳腺癌患者CNB组织免疫组织化学检测结果与手术切除组织的检测结果对比发现,PR、C-erbB-2和Ki-67表达程度差异无统计学意义（P均〉0.05）;ER表达程度差异有统计学意义,CNB组织表达的染色强度（数值）整体强于手术切除组织的检测结果（P〈0.05）,但在定性诊断上两种方法差异无统计学意义（P〉0.05,Kappar值=0.8135）。结论：CNB标本免疫组织化学检测不仅可以准确反映乳腺癌肿瘤ER、PR、CerbB-2和Ki-67的定性表达,而且能准确反映乳腺癌PR、C-erbB-2和Ki-67的表达强度。但是,术前CNB标本ER表达强度整体强于术后切除标本,提示采用术前CNB标本检测ER和手术切除标本检测ER对比的方法评价术前化疗、内分泌治疗对乳腺癌ER表达的影响时,应考虑两者之间原本可能存在的差异。     

ER及PR表达对乳腺癌新辅助化疗疗效的影响

目的 研究雌激素受体(ER)及孕激素受体(PR)的表达对于乳腺癌新辅助化疗(neoadjuvantchemotherapy,NACT)疗效的影响.方法 采用免疫组化法检测52例乳腺癌组织中接受NACT前后的ER及PR的表达,分析ER、PR表达与NACT疗效的关系.结果 ER(-)患者NACT有效率为85.0%(17/20);ER(+)患者为56.3%(18/32),两组间差异有统计学意义(P<0.05);PR(-)患者NACT有效率为80%(21/25),PR(+)患者为51.6%(14/27),两组间差异有统计学意义(P<0.05).结论 ER(-)及PR(-)乳腺癌患者在NACT中的获益分别较ER(+)及PR(+)者明显.测定激素受体的表达状态,可预测乳腺癌患者对NACT是否有效,初步指导肿瘤个体化辅助化疗.     

乳腺癌C-erbB-2、ER及PR的表达与临床病理特征的相关性分析

目的 研究C-erbB-2、雌激素受体(ER)和孕激素受体(PR)在乳腺癌中的表达及其与患者年龄、肿瘤大小、淋巴结转移、组织病理学类型及肿瘤分期的关系和临床意义.方法 应用免疫组化法检测83例乳腺癌中C-erbB-2、ER和PR的表达,分析其与临床病理特征的关系.结果 83例乳腺癌中C-erbB-2、ER和PR的表达阳性率分别为78.3%、56.6%和55.4%.C-erbB-2、ER和PR的表达在患者不同的年龄、肿瘤大小、组织病理学类型及肿瘤分期之间的差异均无统计学意义(P>0.05); ER和PR的表达在有无淋巴结转移之间差异无统计学意义(P>0.05); C-erbB-2的表达在有无淋巴结转移之间的差异有统计学意义(P＜0.05),且它们之间呈正相关(r=0.387,P＜0.05).结论 C-erbB-2是判断乳腺癌淋巴结转移的重要指标之一,联合检测ER和PR更有助于乳腺癌患者的临床治疗和预后判断.     

乳腺癌组织中ER和PR及C-erbB-2的表达及相互关系

近年来随着人民生活水平的提高,乳腺癌发病率呈持续上升趋势,已逐渐跃居女性恶性肿瘤首位.乳腺癌是激素依赖性肿瘤,受雌激素和孕激素调控,多数乳腺组织均有其受体(estrogen receptor,ER;progesterone receptor,PR)的表达.随着分子生物学的不断发展,原癌基因C-erbB-2已被证实对评估乳腺癌预后有蕈要意义.     

维生素D受体在乳腺肿瘤中的表达及其临床意义

目的 探讨维生素D受体(VDR)在乳腺肿瘤中的分布及其与乳腺癌临床病理因素的关系.方法 采用免疫组织化学SP法对51例乳腺癌组织及20例乳腺良性肿瘤组织进行ER,PR,HER2和VDR检测,分析VDR与乳腺癌患者年龄、绝经状况、肿瘤大小、有无腋窝淋巴结转移、临床分期、病理类犁及组织学分级的关系.对VDR与ER,PR及HER2 3种受体在乳腺癌中的表达率以及表达强度之间的关系进行等级相关性分析.结果 VDR在乳腺癌中的表达高于乳腺良性肿瘤(χ~2=4.23,P＜0.05),乳腺癌中VDR的表达强度与PR,HER2的表达强度呈正相关(r_(sPR)=0.295,P＜0.05;r_(sHER2)=0.296,P＜0.05).结论 VDR可能影响乳腺癌的发生;维生素D治疗可能提高PR阳性患者内分泌治疗的效果,改善HER2阳性患者的预后.     

术前针刺活检与手术标本分类的一致性对早期乳腺癌治疗的影响

目的探讨术前针刺活检与手术标本分类的一致性对早期乳腺癌治疗的影响。方法以我院48例接受手术的乳腺肿瘤患者作研究对象,上述患者均接受穿刺活检和手术切除活检,以手术切除活检为标准,分析穿刺组织ER、PR、HER2和Ki-67免疫组化检测结果。结果手术切除确诊42例阳性,6例阴性,穿刺组织ER、PR、HER2和Ki-67的,阳性预测值97.44%、93.75%、89.65%和92.59%,阴性预测值55.56%、25%、15.79%和19.05%,敏感度92.86%、71.43%、61.91%和47.62%,特异度75%、33.33%、27.27%和21.43%。结论穿刺活检ER、PR、HER2和Ki-67免疫组化联合检测比较准确反映乳腺癌组织病理情况,为该病的治疗提供参考。     

乳腺癌病理生物学特性与多肿瘤基因表达的关系

目的 观察多肿瘤基因在乳腺癌组织中的表达,探讨其与乳腺癌病理生物学特性的关系.方法 采用免疫组织化学SP染色法对120例乳腺癌组织中多肿瘤基因的表达进行检测[雌激素受体(ER)、孕激素受体(PR)、表皮生长因子受体(C-erB-2)、p53、转移抑制基因(mn23)、bcl-2、增殖细胞核抗原(PCNA)、多药耐药蛋白(MRP)],分析其与乳腺癌病理生物学特性的关系.结果 p53、bcl-2的表达在不同乳腺癌激素受体状态中差异有统计学意义,且与ER、PR的表达有显著相关性:p53在ER(-)、PR(-)的乳腺癌中呈现高表达,在ER(+)、PR(+)的乳腺癌中呈现低表达(P<0.01);而bcl-2则相反(P<0.01).bcl-2的表达与月经状态有关,在绝经前乳腺癌组织中的表达明显高于绝经后乳腺癌(P<0.01).PCNA的表达与肿瘤的大小相关,在直径较大的肿瘤(>3 cm)中的表达显著高于直径较小的肿瘤(≤3 cm,P<0.01).结论 p53、bcl-2的表达与ER、PR的状态相关,可作为判断乳腺癌生物学特性和预后的重要指标.     

UbcH10在乳腺癌中的表达及意义

目的:探讨UbcH10在乳腺癌中的表达情况及意义.方法:分别运用Western Blot法和免疫组化染色在乳腺癌细胞系和乳腺癌组织芯片中检测UbcH10的表达;统计学分析UbeH10与乳腺癌组织学类型、分化程度、雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)等之间的相关性.结果:UbcH10在MCF-7、MDA-MB-231、MDA-MB-435s等乳腺癌细胞株中均呈阳性表达.在正常乳腺组织中,UbcH10的表达阳性率为0.00%(0/8);而在乳腺癌组织中,总体阳性率为61.25%(49/80,P<0.05),其中浸润性导管癌的阳性表达率为60.42%(29/48,P<0.05).人类表皮生长因子受体2(human epidermal growth factor receptor-type 2,HER2)阴性和阳性组织中UbcH10的表达阳性率分别为46.67%和91.67%(P<0.05),HER2的表达水平与UbcH10表达呈正相关.UbcH10表达与组织级别、年龄、淋巴结转移、ER、PR、BCL2(B-cell CLL/lymphoma 2)、P53等无明显相关性.结论:UbcH10表达在正常乳腺组织和乳腺癌组织中存在明显差别,且其表达与HER2表达呈现正相关关系,可作为判断乳腺癌的潜在标记物,并有望成为乳腺癌靶向治疗中新的靶点.     

Impact of host and histopathological factors on the discrepancies in estrogen receptor,and progesterone receptor,and HER2 status between core needle biopsy and surgically excised tumors

PurposeThe high reliability and utility of core needle biopsy (CNB) have been previously described. Our aim in this study was to clarify the host and histopathological factors influencing the discrepancies in ER, PgR, and HER2 status between CNB and surgically excised tumors (SET).MethodsAll patients diagnosed with operable invasive breast cancer in our hospital between January 2005 and April 2015 were included in the study; patients who required neoadjuvant chemotherapy were excluded. ER, PgR, and HER2 expression were assessed between paired CNB and SET samples. ER and PgR status were determined using immunohistochemistry(IHC). HER2 status was determined using IHC and scored from 0 to 3+. Fluorescence in-situ hybridization analysis was carried out in HER2 2+ cases. The cut off point for ER and PgR positivity was set at 1%.ResultsA total of 1307 patients were assessed. The concordance rates of ER, PgR, and HER2 status in CNB and SET were 95%, 84% and 97%, respectively. Factors of discrepancy were nuclear grade, histological type, and menopausal status for ER and PgR, and none detected for HER2. The discrepancy factors were assessed with univariate and multivariate analysis.ConclusionsUsing the largest known dataset to date of paired samples from a single institution, we evaluated the accuracy of CNB and the discrepancy factors between CNB and SET in breast cancer patients. We conclude that CNB for ER and PgR assessment in postmenopausal patients before treatment should be used with caution. Further research will contribute to increased CNB accuracy, improving patient treatment decisions.     

Breast hormonal receptors test should be repeated on excisional biopsy after negative core needle biopsy

Therapeutic decision-making for women diagnosed with breast cancer requires accurate determination of the estrogen receptor (ER) and progesterone receptor (PR). Decisions about adjuvant therapy are often based on the immunohistochemical (IHC) profile of the core needle biopsy sample (CNB) because the staining is not repeated on the final excisional biopsy (EB). The purpose of this study was to assess the concordance of breast cancer IHC receptor assays on CNB and EB. We identified 176 patients with matching breast CNB and EB that had available ER and PR. While the CNBs were processed and stained in different laboratories, the EB were processed and stained in our institution. The following antibodies were used 1D5, 6F11 and SP1 for ER, and PgR636, 16 and 1E2 for PR, from Dako, Leica and Ventana respectively. Correlation of scores of CNBs with matching EB was analyzed using Spearman correlation coefficients. Sensitivity, specificity, overall agreement and the kappa statistic were used to measure the concordance between CNB and EB. For CNB, there were 141 (80.1%) cases positive for ER and 118 (67%) cases positive for PR. For EB, there were 143 (81.3%) cases positive for ER and 130 (73.9%) cases positive for PR. Overall agreement for ER and PR was seen in 93% (95% CI = 0.88, 0.96) and 90% (95% CI = 0.84, 0.94) respectively. Overall, ER- CNB/ER+ EB was seen in seven (4%) cases and PR- CNB/PR+ EB in 15 (8.5%) cases. ER+ CNB/ER- EB was seen in five (2.8%) cases and PR+ CNB/PR- EB in three (1.7%) cases. To avoid erroneous omission of life-saving endocrine therapy ER and PR should be repeated on the EB for patients whose CNB has negative hormonal receptors.     

新辅助化疗对乳腺癌激素受体、Her-2及Ki67的影响及其临床意义

目的:探讨乳腺癌病人新辅助化疗(NAC)前、后空芯针穿刺活检(CNB)和手术切除(OEB)标本间激素受体(HR),包括雌激素受体(ER)和孕激素受体(PgR),Her-2和Ki67变化及其临床意义。方法:收集2011年1月至2013年10月本中心接受NAC且手术治疗的乳腺癌病人,研究并随访CNB和OEB标本均含有浸润性癌成分的病例。对比CNB与OEB标本间HR、ER、PgR、Her-2和Ki67的相符率和一致性,分析上述受体与NAC疗效和病人预后的关系。结果:本研究共70例。NAC前、后,HR、ER、PgR、Her-2和Ki67的相符率分别为84.3%、82.9%、82.9%、94.3%和70.0%。Ki67一致性较差(κ=0.358),NAC后Ki67表达量显著降低(26.5%比32.1%,P=0.030)。NAC后HR变化病人残留肿瘤Ki67显著高于HR未变化病人(48.3%比22.4%,P=0.031),Ki67表达量降低与NAC临床有效率显著相关。多因素生存分析显示,NAC后HR变化病人3年无病生存率和3年总生存率均低于HR相符病人,激素受体变化是病人早期复发的唯一相关因素(HR=6.133,95%CI:1.399~27.909)。结论:NAC前、后,HR、ER、PgR、Her-2和Ki67等发生改变,其中Her-2较为稳定,需对OEB标本上述受体重复检测。NAC后Ki67表达量下调与NAC疗效呈正相关;HR变化是病人早期复发的独立相关因素;HR变化病人残留肿瘤Ki67较高可能是病人预后较差的原因之一。     

Do the histologic features and results of breast cancer biomarker studies differ between core biopsy and surgical excision specimens?

Core biopsies are commonly used in the diagnosis of breast cancer and often are the only sample for providing prognostic and predictive markers prior to neoadjuvant chemotherapy. We retrospectively studied 87 patients with breast cancer to compare the concordance rates for tumor type, grade, estrogen receptor/progesterone receptor (ER/PR), p53 status and Her2/neu by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) between core and excisional biopsy specimens. The histologic type of cancer had a 100% concordance rate between core and excisional biopsy specimens. The concordance rate of modified Bloom-Richardson score between core and excisional biopsy specimens was 77%, ER was 95%, PR was 89%, and p53 was 86%. The concordance rate for Her2/neu by IHC was 96% and that for FISH was 100% between the core and excisional biopsy specimens. Although breast cancer may have heterogeneous histological and immunohistochemical findings, our study shows that relatively high concordance rates can be obtained when comparing core and excisional biopsy specimens.     

Simultaneous and sequential determinations of steroid hormone receptors in human breast cancer. Influence of intervening therapy.

Estrogen (ER), progesterone (PgR), and androgen (AR) receptors were measured in two simultaneous or subsequent specimens taken each from 259 patients with breast cancer. We studied in 182 patients results from receptor assays, either from one tumor or from the primary tumor, and a lymph node metastasis, and in 77 sequential biopsies with or without intervening therapy. All assays were performed in a single laboratory, considering 10 fmol/mg cytosol protein bound ligand as receptor positive. The concordance rate in simultaneous ER assays was 85%; however, we found a considerable high discordance rate for PgR in primary tumor and lymph node metastasis (25%). The overall discordance rate in sequential biopsies for ER was 38% and for PgR 25%. This discordance rate was primarily dependent on the receptor quality of the first assay (ER+: 50%, ER-: 24%, PgR+: 68%, PgR-: 9%). Considering only the ER+ and PgR+ cases, we found the greatest discordance rate in the patients having endocrine treatment following the first biopsy (55% and 84%, respectively). We conclude that the receptor status of one tumor biopsy is highly representative for other tumor or lymph node biopsies. Because of the high discordance rate of primarily receptor + cases in subsequent recurrences, the receptor quality of these lesions should be analyzed whenever possible.     

A comparative analysis of core needle biopsy and final excision for breast cancer: histology and marker expression

Background

Core needle biopsy (CNB) is used increasingly not only to diagnose breast cancer, but to determine tumor histology, grade and marker expression, select neoadjuvant therapy, and predict sentinel lymph node status. Thus, we undertook this study to evaluate the accuracy of CNB as a predictor of breast cancer histology and marker expression.

Methods

We identified 209 Breast Cancer Registry cases with a preoperative CNB and reviewed all clinicopathologic data for accuracy. Statistical analysis was performed with statistical software.

Results

CNB unequivocally showed cancer in 93%. Exact tumor histology concordance was 86%. Ductal carcinoma in situ on CNB was upgraded to invasive cancer in 23%. Concordance was substantial for estrogen receptor expression (88%, κ = .71), but kappa values were less than .6 for tumor grade, mitotic rate, progesterone receptor (PR), Ki-67, HER-2/neu, and p53 expression.

Conclusions

Reliance on CNB grade and marker expression for critical decision making may be inadvisable. Further study is warranted to optimize breast cancer patient care.     

A comparison of prognostic tumor markers obtained on image-guided breast biopsies and final surgical specimens

BACKGROUND: This study was initiated to determine whether tumor markers obtained on image-guided breast biopsy specimens provide accurate prognostic information for women with invasive breast cancer. METHODS: Prognostic tumor markers on preoperative image-guided biopsy and final surgical specimens were compared in 44 patients with invasive breast cancer. RESULTS: Progesterone receptor (PR) discordance was 18%. In 87% of PR discordant cases, the image-guided biopsy was positive and the final specimen was negative (P = 0.03). Tumor grade was discordant in 36% of patients Discordance for estrogen receptor (ER) = 2%; MIB-1 = 18%; Her2/neu = 9%; EGFR = 10%; p53 = 9%; and bcl-2 = 0%. The discordance for these markers was random and did not reach statistical significance. CONCLUSION: Image-guided core needle biopsies provide reliable information for the majority of prognostic tumor makers. A positive progesterone receptor is significantly more likely to be determined by core biopsy rather than the final surgical specimen. Tumor grade should be based upon the final surgical specimen whenever possible.     

Discordance in early breast cancer for tumour grade, estrogen receptor, progesteron receptors and human epidermal receptor-2 status between core needle biopsy and surgical excisional primary tumour

The aim of the present study was to compare the tumour grade, Estrogen Receptor (ER), Progesteron Receptor (PgR) and Human Epidermal Receptor-2 (HER-2) status in the core needle biopsy (CNB) with those observed in the subsequent excisional primary tumour (EPT).All patients diagnosed with an early breast cancer in our University Hospital Center between January 1, 2005 and December 31, 2006 were included but exclusion criteria of patients with large tumour requiring neoadjuvant chemotherapy and cases with more than one tumour (multicentricity/multifocality tumours). Histological tumour grade assessed according to Nottingham Grading System (SBRm), ER, Pgr and HER-2 tumoural status were assessed twice in CNB and in EPT.A total of 175 patients were assessed. The concordance between CNB and EPT for Grade, ER, PgR and HER2 status were 75.4% (p > 0.00001), 84% (p > 0.00002), 78.3% (p = 0.002) and 98.3% (p = 0.486) respectively.In conclusion CNB can be used with confidence for HER2 determination. For grade, PgR and ER due to substantial discordance results from CNB should be used with caution.     

Relationship between the content of estrogen and progesterone receptors and the pathological characteristics in human breast cancer

Assays of estrogen receptors (ER) and progesterone receptors (PgR) were performed by using the dextran-coated charcoal (DCC) method in 124 cases of invasive breast cancer. The results were correlated with clinical and pathological characteristics. There was no correlation between steroid hormone receptor contents and menopausal status, size of tumor, axillary lymph node status, or histological type. The presences of ER and PgR were significantly correlated with histological grade and its mitotic component. 78.3% of well-differentiated (Grade I) tumors were ER positive. Of this number, 61.1% were also PgR positive. In contrast, 69.0% of poorly differentiated (Grade III) tumors were ER and PgR negative. Tumors with a prominent lymphoid infiltration demonstrated a low frequency of positive ER and PgR. There was a significant inverse correlation between the degree of lymphoid infiltration and histological grade. These results suggest that the ER and PgR status of tumors may indicate a malignancy, and prognostic information can thus be obtained independently of other known factors such as size of the tumor and axillary lymph node status.