Evaluation of serum sialic acid, heat stable alkaline phosphatase and fucose as markers of breast carcinoma

Serum levels of total sialic acid (TSA), lipid bound sialic acid (LSA), heat stable alkaline phosphatase (HSAP) and fucose were measured in 39 patients with breast carcinoma, 14 patients with benign breast diseases and 35 healthy female individuals. Elevated levels of the four biomarkers in breast carcinoma were significant when compared with controls (p less than 0.001). Fucose levels were most sensitive (71.8%), while TSA levels were most specific (64.3%) for breast carcinoma. Sensitivity and specificity were 100% when combinations of LSA with fucose and TSA with HSAP were studied respectively. LSA was significantly elevated in infiltrating duct carcinoma patients compared with lobular carcinoma (p less than 0.001). TSA, HSAP and fucose also had lower mean values in lobular carcinoma as compared to infiltrating duct carcinoma. Increase in the levels of LSA and HSAP after surgical removal of the tumor in breast carcinoma occurred prior to the clinical evidence of the recurrence. The results indicate that the combination of the markers studied might be useful in breast cancer diagnosis and treatment monitoring.     

Estrogen and progesterone receptors in human breast cancer. Correlation with histologic subtype and degree of differentiation

Microscopic review of 490 consecutive human breast biopsy and mastectomy specimens were correlated with estrogen and progesterone receptor content of the tissue, by subtype and degree of differentiation. Of the 4 grades of differentiation, the less differentiated Grade III and IV tumors showed significantly lower levels of estrogen and progesterone receptors in infiltrating ductal and lobular carcinoma (P less than 0.001). In contrast, patients with medullary carcinoma had the lowest tissue levels of estrogen and progesterone receptors with approximately 80% of the cases with less than 10 fmol/mg protein. Patients with mucinous carcinoma had the highest percentages of positive estrogen and progesterone receptor levels (75% and 87%, respectively). Sixty-three percent of the patients with Grade IV infiltrating ductal carcinoma were younger than 53 years of age (P less than 0.001). Patients younger than 53 years of age with Grade II and III infiltrating ductal carcinoma also had significantly lower levels of estrogen receptors, but not of progesterone receptors, than those patients older than 53 years of age (P less than 0.001). Nineteen of 20 "normal" breast tissue specimens were negative (less than 3 fmol/mg protein) for estrogen and progesterone receptors. About 50% of 17 tissue specimens from benign breast lesions (fibroadenoma, fibrocystic disease, sclerosing adenosis) showed positive estrogen (greater than 10 fmol/mg protein) or progesterone receptor values. In two patients with gynecomastia, no estrogen or progesterone receptors were detectable.     

Influence of infiltrating lobular histology on local tumor control in breast cancer patients treated with conservative surgery and radiotherapy

To determine the influence of infiltrating lobular histology on local tumor control, the authors studied 49 patients with Stages I and II infiltrating lobular breast carcinoma treated by limited excision of the tumor and radiotherapy between 1968 and 1981 (median follow-up, 75 months). Results were compared with those in 561 cases of infiltrating ductal carcinoma similarly treated during the same period. The 5-year actuarial risk of local recurrence was similar for patients with infiltrating lobular or ductal carcinoma when the latter was evaluated as a single group (12% versus 11%). However, the 12% 5-year actuarial local recurrence risk for patients with infiltrating lobular carcinoma was intermediate between that for patients with infiltrating ductal carcinomas with an extensive intraductal component (23%) and those without an extensive intraductal component (5%). The pattern of recurrence in the breast was similar in the infiltrating lobular and ductal groups. All recurrences in patients with infiltrating lobular carcinoma and 80% of recurrences in the infiltrating ductal group occurred in the vicinity of the primary tumor (P = not significant). None of the clinical or morphologic features examined significantly influenced the risk of local recurrence in patients with infiltrating lobular carcinoma. The authors conclude that combined conservative surgery and radiotherapy appear to be a reasonable treatment option for patients with infiltrating lobular carcinoma, but further follow-up will be required to confirm these results.     

Serum trace elements and Cu/Zn ratio in breast cancer patients

Serum copper, zinc, and the Cu/Zn ratio were measured in 55 patients with breast disease (20 with benign breast diseases and 35 patients with breast cancer) and 30 controls. The mean serum copper levels were higher in breast cancer than in benign breast diseases (167.3 micrograms/dl vs. 117.6 micrograms/dl) (P less than 0.001) and controls (167.3 micrograms/dl vs. 98.8 micrograms/dl) (P less than 0.001). Patients with advanced breast cancer had higher serum copper levels than did patients with early breast cancer (177.9 micrograms/dl vs. 130.4 micrograms/dl) (P less than 0.001). The mean serum zinc levels were lowered only in patients with advanced breast cancer as compared with controls (88.6 micrograms/dl vs. 115.1 micrograms/dl) (P less than 0.001). Serum zinc levels were not decreased in patients with early breast cancer and benign breast diseases. The Cu/Zn ratio was increased in breast cancer patients (1.91 vs. 0.86) (P less than 0.001) but not in patients with benign breast diseases. The precise mechanisms responsible for the alterations in trace element levels in breast cancer patients are still unclear and require further evaluation. However, the serum copper levels and the Cu/Zn ratio may be used as biochemical markers in these patients.     

Spectral morphometric characterization of breast carcinoma cells

The spectral morphometric characteristics of standard haematoxylin and eosin breast carcinoma specimens were evaluated by light microscopy combined with a spectral imaging system. Light intensity at each wavelength in the range of 450-800 nm was recorded for 10(4) pixels from each field and represented as transmitted light spectra. A library of six characteristic spectra served to scan the cells and reconstruct new images depicting the nuclear area occupied by each spectrum. Fifteen cases of infiltrating ductal carcinoma and six cases of lobular carcinoma were examined; nine of the infiltrating ductal carcinoma and three of the lobular carcinoma showed an in situ component. The spectral morphometric analysis revealed a correlation between specific patterns of spectra and different groups of breast carcinoma cells. The most consistent result was that lobular carcinoma cells of in situ and infiltrating components from all patients showed a similar spectral pattern, whereas ductal carcinoma cells displayed spectral variety. Comparison of the in situ and the infiltrating ductal solid, cribriform and comedo carcinoma cells from the same patient revealed a strong similarity of the spectral elements and their relative distribution in the nucleus. The spectrum designated as number 5 in the library incorporated more than 40% of the nuclear area in 74.08% of the infiltrating lobular cells and in 13.64% of the infiltrating ductal carcinoma cells (P < 0.001). Spectrum number 2 appeared in all infiltrating ductal cells examined and in none of the lobular cells. These results indicate that spectrum number 5 is related to infiltrating lobular carcinoma, whereas spectrum number 2 is characteristic for infiltrating ductal carcinoma cells. Spectral similarity mapping of central necrotic regions of comedo type in situ carcinoma revealed nuclear fragmentation into defined segments composed of highly condensed chromatin. We conclude that the spectral morphometric features found for lobular and ductal cell populations may serve future automated histological diagnostics.     

The distribution of carcinoembryonic antigen in breast carcinoma. Diagnostic and prognostic implications

Carcinoembryonic antigen (CEA) has been shown to be a useful tumor marker in patients with breast carcinoma. The unlabeled antibody immunoperoxidase technique was used to localize CEA in 93 cases of primary breast carcinoma, 15 cases of atypical duct papillomatosis, and 4 cases of duct papilloma. Normal breast epithelium and breast epithelium in fibrocystic disease did not stain positively for CEA. Twenty-four of 27 (88%) intraductal carcinomas, and 47 of 69 (68%) infiltrating duct carcinomas were CEA positive. In contrast, only 5 of 21 (23%) in situ lobular carcinomas and 8 of 24 (33%) infiltrating lobular carcinomas were positive for CEA. All 15 cases of atypical epithelial papillomatosis were negative, whereas 1 of the 4 cases of duct papilloma exhibited microscopic foci of weak CEA positivity. There was a trend for infiltrating duct carcinomas, 3 cm in diameter or smaller, staining strongly positive for CEA, to be associated with synchronous axillary lymph node metastases (P = 0.09). Tumor heterogeneity was a constant feature of CEA staining with positivity varying from region to region and even from cell to cell. Positive immunohistochemical staining for CEA may play an adjunctive role in discriminating intraductal carcinoma from atypical papillary ductal proliferations.     

The use of CA-50 radioimmunoassay inhibition test in the differential diagnosis of benign and malignant breast disease

The role of the tumour marker CA-50 has been studied in the differential diagnosis of benign and malignant breast disease. Serum levels of CA-50 were determined by radioimmunoassay using a level of 17 units/ml as a cut-off. All 50 normal subjects and 22 of 24 patients (92%) with benign breast disease had CA-50 levels below 17 units/ml. By contrast, 15 of 36 patients (42%) with breast carcinoma had serum CA-50 levels above 17 units/ml (P less than 0.001). There was no clear correlation with tumour stage. The data suggest that CA-50 levels may help to differentiate benign and malignant diseases of the breast.     

乳腺肿瘤中c-erbB-2和nm23蛋白的表达及临床意义

 目的　研究c erbB 2和nm2 3基因蛋白在乳腺肿瘤中的表达情况及临床意义。方法应用免疫组化S P法 ,对 131例乳腺良恶性肿瘤进行c erbB 2和nm2 3基因蛋白检测 ,对其中 10 2例乳腺癌进行雌激素受体 (ER)和孕激素受体 (PR)检测。结果　c erbB 2蛋白在导管内癌、Paget病及浸润性导管癌中呈高表达 ;nm2 3蛋白在浸润性小叶癌中呈高表达。c erbB 2与淋巴结转移及PR呈正相关 ;nm2 3与乳腺癌患者的年龄、组织学分级、淋巴结转移及ER和PR密切相关。结论c erbB 2呈阴性表达、而nm2 3呈阳性表达时乳腺癌患者的预后最好。     

Breast cancer detection by dedicated breast positron emission tomography according to the World Health Organization classification of breast tumors

ObjectiveConsidering the difficulty in detecting primary breast cancers using whole-body positron emission tomography (WBPET) owing to its limited spatial resolution, we aimed to evaluate the detectability of breast cancer by ring-type dedicated breast PET (DbPET) on the World Health Organization (WHO) histological classification in comparison with WBPET.MethodsA total of 938 patients with breast cancer underwent WBPET and ring-type DbPET, and 1021 lesions were histologically assessed based on the WHO classification of tumors of the breast. The findings of WBPET and DbPET were retrospectively evaluated and compared.ResultsThe size-related sensitivity of DbPET was superior to that of WBPET for subcentimetric tumors (81.9% vs. 52.4%, P < 0.001). The histological distribution was as follows: 11 lobular carcinoma in situ, 158 ductal carcinoma in situ, 738 infiltrating duct carcinoma not otherwise specified (NOS), 12 lobular carcinoma NOS, 40 mucinous adenocarcinoma, 13 tubular carcinoma, 36 invasive breast carcinoma others, and 13 papillary neoplasms. WBPET had low sensitivity for lobular carcinoma in situ, ductal carcinoma in situ, lobular carcinoma NOS, mucinous adenocarcinoma, and tubular carcinoma. DbPET showed improved sensitivity for all the above except lobular and tubular carcinoma. The maximum standardized uptake values (SUVmax) of DbPET were significantly higher than those of WBPET for histological types, excluding lobular carcinoma in situ. The SUVmax of papillary neoplasms was high regardless of low-grade histology and Ki-67 labeling index.ConclusionsDBPET was found to have high sensitivity and SUVmax values for all histologic types that showed low sensitivity of detection on WBPET, except lobular carcinoma in situ.     

The influence of infiltrating lobular carcinoma on the outcome of patients treated with breast-conserving surgery and radiation therapy

Background: The role of conservative surgery and radiation therapy (CS and RT) in the treatment of patients with infiltrating ductal carcinoma is well established. However, the efficacy of CS and RT for patients with infiltrating lobular carcinoma is less well documented. The goal of this study was to examine treatment outcome after CS and RT for patients with infiltrating lobular carcinoma and to compare the results to those of patients with infiltrating ductal carcinoma and patients with mixed ductal–lobular histology. Methods: Between 1970 and 1986, 1624 patients with Stage I or II invasive breast cancer were treated with CS and RT consisting of a complete gross excision of the tumor and 6000cGy to the primary site. Slides were available for review for 1337 of these patients (82%). Of these, 93 had infiltrating lobular carcinoma, 1089 had infiltrating ductal carcinoma, and 59 had tumors with mixed ductal and lobular feature these patients constitute the study population. The median follow-up time for surviving patients was 133 months. A comprehensive list of clinical and pathologic features was evaluated for all patients. Additional histologic features assessed for patients with infiltrating lobular carcinoma included histologic subtype, multifocal invasion, stromal desmoplasia, and the presence of signet ring cells. Results: Five and 10-year crude results by site of first failure were similar for patients with infiltrating lobular, infiltrating ductal, and mixed histology. In particular, the 10-year crude local recurrence rates were 15%, 13%, and l3% for patients with infiltrating lobular, infiltrating ductal, and mixed histology, respectively. Ten-year distant/regional recurrence rates were 22%, 23%, and 20% for the three groups, respectively. In addition, the 10-year crude contralateral breast cancer rates were 4%, 13% and 6% for patients with infiltrating lobular, infiltrating ductal and mixed histology, respectively. In a multiple regression analysis which included established prognostic factors, histologic type was not significantly associated with either survival or time to recurrence. Conclusions: Patients with infiltrating lobular carcinoma have a similar outcome following CS and RT to patients with infiltrating ductal carcinoma and to patients with tumors that have mixed ductal and lobular features. We conclude that the presence of infiltrating lobular histology should not influence decisions regarding local therapy in patients with Stage I and II breast cancer.     

Infiltrating lobular carcinoma of the breast: Response to endocrine therapy and survival

The records of 480 patients who received systemic therapy for advanced breast cancer in the University Hospital of South Manchester from 1975 to 1983 were examined. There were 264 with infiltrating duct carcinomas (IDC) and 33 with infiltrating lobular carcinomas (ILC) for whom the response to endocrine therapy was known. There were 92 responses (35%) among the IDC patients and 9 (27%) among the ILC patients. Sixty-seven per cent of IDC patients tested had steroid hormone receptor positive tumours compared to 90% for ILC (P < 0.001). Comparison of survival from diagnosis, disease free interval and survival from relapse showed no significant differences between the two groups. Thus despite almost of ILC patients having hormone receptor positive tumours their survival was similar to that of IDC patients. This appears to be due to a lower than expected response rate to endocrine therapy. This is a further indication of the different biological characteristics of these two histological sub-types of breast carcinoma.     

乳腺肿瘤中C—erbB—2癌基因蛋白的表达及意义

目的：探讨Ｃ－ｅｒｂＢ－２癌基因蛋白在乳腺中肿瘤中的表达情况及临床意义。方法：应用免疫组化ＳＰ法,对１２６例乳腺良恶性肿瘤进行Ｃ－ｅｒｂＢ－２癌基因蛋白检测,其中９７例乳腺癌进行激素受体（ＥＲ）和孕激素受体（ＰＲ）检测。结果：Ｃ－ｅｒｂＢ－２蛋白阳性表达的细胞主要为癌细胞。Ｃ－ｅｒｂＢ－２蛋白在导管内癌、Ｐａｇｅｔ‘ｓ蛋白在导管内癌Ｐａｇｅｔ’ｓ病是浸润性导管癌中呈高表达,在浸润的小叶癌中均呈阴性     

二甲基苯蒽诱发大鼠乳腺癌的组织形态学和微血管密度观察

目的：研究诱发性大鼠乳腺癌发生过程中组织形态学变化和肿瘤微血管密度（MVD）。方法：Wistar雌性大鼠85只,SD雌性大鼠22只,配制浓度为10 mg/ml的二甲基苯蒽（DMBA）麻油溶液灌胃大鼠。17只大鼠8周前死亡,剩余90只大鼠从第8周开始至24周,每2周取大鼠10只活杀,观察乳腺外形,取乳腺肿块HE染色和Ⅷ因子相关抗原免疫组化染色。结果：存活8周以上的90只大鼠中,73只成功诱发乳腺肿瘤,其中乳腺良性增生11只,乳腺癌62只。乳腺癌62只大鼠中,浸润性导管癌35只,浸润性小叶癌15只,乳头状腺癌5只,其他类型肿瘤7只。乳腺癌分化程度分级为：高分化5只,中分化36只,低分化21只。乳腺癌MVD平均值为（6.53±2.71）个/高倍视野,乳腺良性增生MVD为（1.67±0.95）个/高倍视野,乳腺癌MVD显著高于乳腺增生性疾病（P〈0.01）。低分化乳腺癌MVD显著高于中、高分化乳腺癌（P〈0.001）。结论：DMBA灌胃Wistar雌性大鼠乳腺癌诱发成功率高,肿瘤分化程度与微血管密度密切相关。     

Serum glycoconjugates in patients with anemia and myeloid leukemia

Because of carbohydrate alterations in malignant cells, serum glycoproteins have drawn considerable attention. In the current investigation we determined total sialic acid (TSA), lipid bound sialic acid (LSA), protein bound hexoses (galactose + mannose), fucose, hexosamines (galactosamine + glucosamine) and mucoid protein concentrations in the serum of patients with anemia and myeloid leukemia. The results were compared with those obtained in healthy individuals. In the leukemia patients we observed significant increases in glycoconjugates compared with the controls (P less than 0.001), and in TSA and fucose levels compared with the anemia patients (P less than 0.001). LSA and hexosamine levels were significantly lower in anemia patients with respect to the leukemia patients (P less than 0.01 and P less than 0.05 respectively), whereas levels of mucoid proteins and hexoses did not show significant differences. Except for hexosamines, all the markers tested were significantly elevated in the anemia patients compared with the controls. The present study suggests that the glycoconjugates investigated might be useful biochemical markers for differentiating anemic from leukemic conditions.     

伴印戒细胞成分乳腺癌的临床病理学观察

目的　探讨伴印戒细胞成分乳腺癌的病理特征及诊断 ,鉴别诊断要点。方法　经HE、AB/PAS及免疫组化对 8例伴印戒细胞成分乳腺癌进行观察 ,并文献复习。结果　本组患者均为女性 ,平均年龄 5 4 6岁 ,肿块平均 2 6cm ;组织学以浸润性乳腺癌伴多少不等的典型印戒样癌细胞为特征 ,6 / 8例为浸润性小叶癌 ,其中 5 / 6例ER、PR阳性表达 ;2 / 8例浸润性导管癌 ,1/ 2例ER、PR阳性 ;7/8例癌细胞中印戒细胞成分超过 10 %;4例做AB/PAS均提示印戒细胞浆内的粘液表达 ;印戒细胞成分的多少与病人预后有关系。结论　伴印戒细胞成分乳腺癌是乳腺癌中的一种特殊类型 ,排除转移及与粘液腺癌的鉴别诊断尤为重要。     

二甲基苯蒽诱发大鼠乳腺癌的组织形态学和微血管密度观察

目的:研究诱发性大鼠乳腺癌发生过程中组织形态学变化和肿瘤微血管密度(MVD).方法:Wistar雌性大鼠85只,SD雌性大鼠22只,配制浓度为10 mg/ml的二甲基苯蒽(DMBA)麻油溶液灌胃大鼠.17只大鼠8周前死亡,剩余90只大鼠从第8周开始至24周,每2周取大鼠10只活杀,观察乳腺外形,取乳腺肿块HE染色和Ⅷ因子相关抗原免疫组化染色.结果:存活8周以上的90只大鼠中,73只成功诱发乳腺肿瘤,其中乳腺良性增生11只,乳腺癌62只.乳腺癌62只大鼠中,浸润性导管癌35只,浸润性小叶癌15只,乳头状腺癌5只,其他类型肿瘤7只.乳腺癌分化程度分级为:高分化5只,中分化36只,低分化21只.乳腺癌MVD平均值为(6.53±2.71)个/高倍视野,乳腺良性增生MVD为(1.67±0.95)个/高倍视野,乳腺癌MVD显著高于乳腺增生性疾病(P<0.01).低分化乳腺癌MVD显著高于中、高分化乳腺癌(P<0.001).结论:DMBA灌胃Wistar雌性大鼠乳腺癌诱发成功率高,肿瘤分化程度与微血管密度密切相关.     

乳腺癌中MUC2和MMP-9的表达及其临床意义

  目的  探讨MUC2和MMP-9在乳腺癌中的表达及其与临床病理特征之间的关系。   方法  应用逆转录-聚合酶链反应（RT-PCR）方法检测68例乳腺良性疾病和186例乳腺癌中MUC2和MMP-9基因的表达,免疫印迹法观测MUC2和MMP-9蛋白表达情况。分析两者与乳腺癌临床病理特征之间的关系及两者的相关性。   结果  MUC2和MMP-9 mRNA在乳腺癌中的表达明显高于乳腺良性疾病组。乳腺良性疾病组织中MUC2和MMP-9 mRNA的表达率分别为2.9%（2/68）、13.2%（9/68）,均显著低于癌组织39.8%（53/186）、73.1%（136/186）（P < 0.05）。类似于基因表达,MUC2和MMP-9蛋白在乳腺癌中的表达相对较高。MUC2和MMP-9基因在乳腺癌中的表达与病理类型、淋巴结转移相关（P < 0.05）,MMP-9表达还与肿瘤大小和组织学分级有关（P < 0.05）,两者均与患者年龄无关（P>0.05）。乳腺癌组织中MUC2和MMP-9 mRNA的表达呈负相关（r=-0.814,P < 0.001）。   结论  MUC2和MMP-9联合检测可作为诊断乳腺疾病的指标之一,为乳腺癌诊断和治疗提供参考。      

c-erbB-2、nm 23及PCNA蛋白在乳腺肿瘤中的表达及意义

目的探讨c-erbB-2、nm23及PCNA蛋白在乳腺肿瘤中的表达情况及意义.方法应用免疫组化S-P法,对131例乳腺良恶性肿瘤进行c-erbB-2、nm23和PCNA蛋白检测,对其中102例乳腺癌进行雌激素受体(ER)和孕激素受体(PR)检测.结果c-erbB-2蛋白在导管内癌、Paget病及浸润性导管癌中呈高表达;nm23蛋白在浸润性小叶癌中呈高表达;PCNA在导管内癌、髓样癌及粘液腺癌中呈高表达.c-erbB-2与淋巴结转移及PR呈正相关;nm23与乳腺癌患者的年龄、组织学分级、淋巴结转移及ER和PR密切相关.PCNA与肿瘤组织的坏死明显相关.结论不同组织学类型的乳腺肿瘤可能由不同的癌基因以不同的组合方式发生突变所致.c-erbB-2呈阴性表达而nm23呈阳性表达时,乳腺癌患者的预后最好.     

6 207例乳腺肿瘤临床病理资料分析

 目的 探讨1981～2007年27年来乳腺肿瘤发病趋势特点和变化规律,为临床和病理医师提供有价值的参考。 方法 选自天津医科大学总医院病理科1981～2007年外科手术活检病理档案中的乳腺原发肿瘤6 207例,应用SAS6.0统计软件包对该资料进行统计分析。 结果 27年来乳腺肿瘤占肿瘤总数百分比呈上升趋势（P=0.005）,乳腺恶性肿瘤占恶性肿瘤百分比虽然有所波动,但总体呈上升趋势（P=0.027）。三个年代乳腺良、恶性肿瘤发病平均年龄有增高趋势。三个年代乳腺肿瘤组织学类型也有所变化,乳腺良性肿瘤中,纤维腺瘤和导管内乳头状瘤构成比增加,腺瘤和间叶性肿瘤构成比下降。乳腺恶性肿瘤中,浸润性导管癌仍是主要类型,但导管内癌构成比增加,腺癌和髓样癌有所下降。青年组、中年组和老年组乳腺良、恶性肿瘤组织学类型差异均有统计学意义 （P<0.001）,良性肿瘤中青年组纤维腺瘤构成比高于中老年组,而导管内乳头状瘤和间叶性肿瘤构成比低于中老年组。恶性肿瘤中青年组恶性叶状肿瘤及浸润性小叶癌高于老年组。 结论 乳腺肿瘤检出率增加,尤其是乳腺恶性肿瘤检出率增加明显,组织学类型也有所变化,应引起临床和病理医师的注意。     

Carcinomatous meningitis associated with infiltrating lobular carcinoma of the breast

The records of 365 patients with advanced carcinoma of the breast were examined to identify those with CNS involvement. Nineteen (5.2%) developed parenchymal cerebral deposits and 10 (2.7%) developed meningeal infiltration during the course of their disease. Parenchymal cerebral deposits were almost exclusively associated with infiltrating duct carcinoma (95%) and meningeal infiltration (carcinomatous meningitis) was almost exclusively associated with infiltrating lobular carcinoma. Meningeal infiltration occurred late in the course of advanced disease and was associated with diffuse involvement of the bone marrow and abdominal structures.