白蛋白与纤维蛋白原表达比对230例乳腺浸润性导管癌预后影响分析

目的选择合适的预后指标对提高乳腺癌患者的生活质量具有重要意义。本研究探讨白蛋白与纤维蛋白原比(albumin to fibrinogen ratio,AFR)在乳腺浸润性导管癌组织中的表达及预后意义。方法选取河北医科大学第四医院乳腺中心2009-01-01-2012-04-30行手术切除的230例原发性乳腺浸润性导管癌患者石蜡包埋组织为研究对象,收集术前患者血清的纤维蛋白原和白蛋白数值,并采用Kaplan-Meier法及Cox比例回归风险模型进行生存分析,探讨AFR表达与无病生存率(disease free survival,DFS)的关系,并根据多因素结果,将P <0.05建立DFS预后模型。结果 AFR采用二分类法,将AFR分为2组,当AFR≥13.1时,无病生存期为(59.97±17.19)个月,当AFR<13.1时,无病生存期为(65.30±13.74)个月,二者相比差异有统计学意义,Z=1.178,P=0.010。单因素分析结果表明红细胞(Wald=3.962,P=0.047)、AFR(Wald=44.042,P=0.008)、TNM(Wald=6.754,Ⅰ期与Ⅱ期P=0.016,Ⅰ期与Ⅲ期P=0.014)、核分级(Wald=16.947,1级与2级P=0.099,1级与3级P=0.001)、p53(Wald=19.481,<25%与≥25%~<50%P=0.471,<25%与≥50%~<75%P=0.072,<25%与≥75%P=0.014)、Ki-67(Wald=9.223,P=0.002)及脉管瘤栓(Wald=21.171,P<0.001)与无病生存期相关。多因素结果表明AFR(HR=1.346,95%CI为1.107~1.636,P=0.003)、TNM(Ⅰ期与Ⅱ期HR=5.604,95%CI为1.859~16.891,P=0.002;Ⅰ期与Ⅲ期HR=3.674,95%CI为0.856~15.766,P=0.080)、核分级(1级与2级HR=4.450,95%CI为0.749~26.447,P=0.101;1级与3级HR=25.315,95%CI为3.483~183.984,P=0.001)、p53(<25%与≥25%~<50%HR=0.343,95%CI为0.100~1.174,P=0.088;<25%与≥50%~<75%HR=0.051,95%CI为0.009~0.308,P=0.001;<25%与≥75%HR=6.235,95%CI为2.112~18.405,P<0.001)、Ki-67(HR=7.934,95%CI为1.483~42.457,P=0.016)及脉管瘤栓(HR=11.336,95%CI为4.602~27.924,P<0.001)与无病生存期相关,以多因素分析里P<0.05的因素为变量建立乳腺浸润性导管癌患者DFS预后模型,预测患者3年及5年DFS,模型受试者工作特征曲线(receiver operating characteristic curve,ROC)下面积为0.834。结论 AFR低表达是改善乳腺癌DFS的独立预后因素,预后模型预测效能良好。

Accessory Breast Cancer Occurring Concurrently with Bilateral Primary Invasive Breast Carcinomas:A Report of Two Cases and Literature Review

The development of accessory breast tissue,which is found anywhere along the milk line,is attributed to the failure of milk line remnants to regress during embryogenesis.Primary tumors may arise from any ectopic breast tissue.Accessory breast cancer occurring concurrently with primary invasive breast cancer is extremely rare.Two such cases were reported in this article.One was a 43-year-old Chinese female who exhibited bilateral breast cancer(invasive ductal carcinoma,not otherwise specified,IDC-NOS) and an accessory breast carcinoma(IDC-NOS) incidentally identified in her left axilla.The ectopic breast tissue in her right axilla presented with adenosis.The patient was surgically treated,followed by postoperative docetaxel epirubicin(TE) chemotherapy.The second case was a 53-year-old Chinese female with bilateral breast cancer(apocrine carcinoma) accompanied by an accessory breast carcinoma(IDC-NOS) in her right axilla that was also incidentally identified.The patient was surgically treated after three doses of cyclophosphamide epirubicin docetaxel(CET) neoadjuvant chemotherapy,followed by adjuvant chemotherapy of the same regimen.

Clinical and pathological characteristics of intraductal proliferative lesions and coexist with invasive ductal carcinomas

Objective： The purpose of this study was to study the clinical and pathological characteristics of breast intraductal proliferative lesions （IDPLs） and associated with invasive breast cancer. Methods： We reviewed 327 cases of breast intra- ductal proliferative lesions including 53 cases of usual ductal hyperplasia, 57 cases of atypical ductal hyperplasia, 89 cases of ductal carcinoma in situ, and 128 cases coexist with invasive ductal carcinomas. Cases of pure invasive cancer without intraductal proliferative lesions were excluded. The mult IDPLs biological parameters including the express of ER, PR, HER2, HIF-lo and Ki-67 detected by immunohistochemistry S-P method （n = 327） and the levels of CA153, TSGF, CA125 and CEA both in nipple discharge and serum （n = 179） measured with Electrochemiluminescence method and their relationship were studied, and 30 cases of normal pregnant women were compared with. Results： A single histologic subtype was present in 49.85% （163/327） of the cases, two subtypes in 33.03% （108/327）, and three in 17.13% （56/327）. The most common subtypes present were cribriform （43.12%, 141/327） and solid （38.53%, 126/327）, while the comedo （16.35%, 54/327）, and micropapillary （12.84%, 42/327） subtypes were less common. Comedo and solid were frequently found together for coexpres- sion as were micropapillary and papillary subtypes. However, Comedo subtype was much less likely to be found with papillary, cribriform or micropapillary subtypes. Additionally, comedo subtypes tend to be hormone receptor negative, Her2 positive and high-grade while the cribriform and solid subtype tends to be hormone receptor positive, Her2 negative and low grade. Papil- lary subtype was least likely to be associated with an invasive cancer. Furthermore, the nipple discharge and serum levels of CA153, TSGF, CA125 and CEA in coexist with invasive ductal carcinomas patients were significantly higher than those in the benign breast disease （pure intraductal proliferative lesions） and normal pregnant women （P 〈 0.01）. Additionally, the levels of CA153, TSGF, CA125 and CEA in nipple discharge were significantly higher than in the serum （P 〈 0.01）, and had a positive correlation with the Ki-67, grade, clinical stage, lymph node metastasis and tumor recurrence （P 〈 0.05）, and negative correla- tion with the level of ER and PR （P 〈 0.05）. The sensitivity of the four serum tumor markers in combination was only 69.77%, in contrast, the combined detection both in discharge and serum was 97.67%, and the negative predictive value was 99.03%. The sensitivity of combined detection both in nipple discharge and serum were significantly higher than other detection （P 〈 0.05）. Conclusion： IDPLs often present more than one histologic subtype and the most common subtypes are cribriform and solid, while comedo and micropapillary subtypes are less common. Our results suggest that the levels of CA153, TSGF, CA125 and CEA in nipple discharge were significantly higher than those in the serum, and is associated with HIF-le. The aberration of HIF-la may play a key role during oncogenesis and promote breast cellular transformation into malignancy, a finding useful for further understanding of tumorigenesis. Nipple discharge can be the earliest presenting symptom of breast cancer. The dynamic combined detection of the four tumor markers both in nipple discharge and serum are helpful to the stratification of preoperative patients and benefit to better prewarning markers for monitoring their recurrence and metastasis and clinical staging of tumors in clinic, but cannot increase the sensitivity of judging the patients with early breast cancer.

Low-Grade and High-Grade Invasive Ductal Carcinomas of the Breast Follow Divergent routes of Progression

Low-grade invasive ductal carcinoma is almost diploid, and has frequent losses of chromosome 16q, which is shared by other precancerous lesions of the mammary gland such as flat epithelial atypia （FEA）, atypical ductal hyperplasia （ADH）, and lownuclear grade ductal carcinoma in situ （DCIS）. The genetic alterations accumulate in a stepwise fashion as the precancerous lesions progress to invasve ductal carcinoma. This supports the linear progression model of breast cancer from FEA, through ADH, to low- nuclear grade DCIS as non-obligate early events in low-grade IDC evolution. In contrast, high-grade carcinoma tends to aneuploidy with complex genetic alterations--most importantly, frequent gains at chromosome 16q. Frequent losses at chromosome 16q in low-grade IDC and gains in the same arm of the same chromosome in high-grade IDC imply that these lesions are two end outcomes of different disease processes and that they do not lie in the same continuum of a process. Therefore, low-grade and high-grade IDC are two distinct diseases with a divergent route of progression.

Clinical signification of high-mobility group box 1protein(HMGB1) expression in infiltrating ductalcarcinoma breast tissue

Objective: Exploring the clinical signification of high-mobility group box 1 protein(HMGB1) expression in infiltrating ductal carcinoma(IDC) breast tissue. Methods: The expression of HMGB1 protein in IDC breast tissue was detected by immunohistochemistry, and the relations among size of tumour, lymph node metastasis, clinical staging, estrogen receptor(ER), progesterone receptor(PR) and human epidermal growth factor receptor 2(HER-2) were also analyzed. Results: Fortysix cases out of 60 cases of IDC breast tissue showed positive or strong positive HMGB1 expression(76.67%), statistical significance was observed between HMGB1 expression with clinical staging(P < 0.01), lymph node metastasis(P < 0.01), breast cancer ER(P < 0.05) and HER-2(P < 0.05), however same conclusion can not be drawn between HMGB1 with either size of tumour or PR expression(P > 0.05) in IDC breast tissue. Spearman analysis showed negative correlation between HMGB1 expression and ER, and positive correlation between HMGB1 expression and clinical staging, lymph node metastasis together with HER-2. Conclusion: It's promising that HMGB1 expression in IDC tissue can be one of biological indicators of poor prognosis.