The expression of Fhit protein is related inversely to disease progression in patients with breast carcinoma

BACKGROUND: The FHIT gene, located at human chromosome 3p14.2, frequently is deleted in a number of human tumors, including breast carcinoma. Its protein product (Fhit) is presumed to have tumor suppressor function. Loss of expression of a tumor suppressor gene is an important step in tumor progression from premalignant, to in situ, to invasive carcinoma. METHODS: In the current study, Fhit expression was examined in invasive carcinomas and in epithelial lesions representing stages of carcinoma progression in 50 mastectomy specimens using immunohistochemical methods. RESULTS: Normal ductal and lobular epithelium consistently and strongly expressed Fhit. A complete loss of or a significant reduction in Fhit expression was observed in 72% of breast carcinomas. A statistically significant, negative correlation in Fhit expression among the stages of disease progression in Fhit negative breast carcinomas was observed (normal epithelium > hyperplasia > atypical hyperplasia and carcinoma in situ > invasive carcinoma), whereas no loss of Fhit expression in precursor lesions was observed in Fhit positive tumors. CONCLUSIONS: These observations are consistent with the observed role of FHIT as a tumor suppressor gene in the pathogenesis of specific subsets of carcinomas.     

p63 expression in normal,hyperplastic and malignant breast tissues

BACKGROUND: p63 is a homologue of the p53 tumor suppressor gene and its protein is selectively expressed in the basal cells of a variety of epithelial tissues. It has recently been confirmed that p63 is expressed in the basal cells of normal prostate glands but not in prostatic carcinomas. Whether expression of p63 in breast correlates with tumor progression is the focus of this study. METHODS: Forty cases, which all contained normal breast tissue, ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma in the same patient were included in this investigation using an indirect immunohistochemical method and double staining. RESULTS: p63 was exclusively expressed in the myoepithelial cells of normal breast, partially expressed in ductal hyperplasia, rarely expressed in carcinoma in situ and not expressed in invasive carcinomas. CONCLUSION: The results suggest an association between loss of p63 expression and progression of breast ductal carcinoma. p63 immunostaining might be of assistance for distinguishing invasive ductal carcinoma from ductal carcinoma in situ or rare questionable ductal hyperplastic lesions, leading to correct therapy clinically.     

Radial scars in women with breast cancer

In 84 consecutive autopsies of women with a clinical diagnosis of invasive breast cancer, radial scars were found in the contralateral breast in 35 cases (42%) by an extensive histopathologic method. Four women had radial scars on the ipsilateral side in the breast tissue available from the primary surgical procedure or at autopsy. One woman had an invasive breast cancer with morphologic features compatible with but not diagnostic of transition from a radial scar. Of the six radial scars with carcinoma in situ occurring in three women, three were of ductal and three of lobular type. In the remaining cases only radial scars with a benign appearance were found except for two with atypical hyperplasia. The frequency of radial scars was significantly higher in women with fibrocystic disease (55%) compared to women without (24%). Contralateral primary invasive and in situ breast cancer occurred in 68%. No difference in the frequency of radial scars in women with and without breast cancer was found and radial scars were not associated with any specific type of breast cancer. Our findings do not indicate a higher malignant potential of radial scars than of fibrocystic disease. It is suggested that only radial scars containing high-risk epithelial changes such as atypical hyperplasia and carcinoma in situ are associated with an increased risk of subsequent breast cancer development.     

The histopathology of non-palpable breast lesions detected by clinical mammography

An histological study of 227 non-palpable breast lesions detected by clinical mammography revealed 64 invasive carcinomas at a mean patient age of 60.5 years. There were 10 carcinomas in situ, mean age 57.2 years. Fibrocystic disease with intraductal epithelial hyperplasia was found in 41 specimens, mean age 54.3 years. Fibrocystic disease without intraductal hyperplasia was found in 57 biopsies, mean age 50.7 years. Histological microcalcifications were found in 113 biopsies, and were considered to be a marker for epithelial proliferation of both benign and malignant kinds. Microcalcifications detectable in histological sections and by mammography differ in size by a factor of 10 or more. This difference has to be considered when comparing histological and mammographic findings.     

乳腺导管内增生性病变中 ERα基因启动子甲基化的探讨

目的：研究与乳腺浸润性导管癌风险密切相关的导管内增生性病变中 ERα基因启动子区甲基化情况。方法：用甲基化特异性 PCR 研究140例乳腺导管内增生性病变（UDH 40例、ADH 63例、DCIS 37例）的ERα第1、3、4、5启动子甲基化情况。结果：55．0％（22／40）UDH 出现 ERα基因启动子甲基化,11．1％（7／63） ADH 出现 ERα基因启动子甲基化,43．2％（16／37）DCIS 出现 ERα基因启动子甲基化,三者间差异显著（P ＜0．05）。结论：ERα基因启动子甲基化在乳腺癌的发生发展中是动态变化的,也许其并非是所有分子亚型乳腺癌的始动因素,但这个过程对于细胞的生物学行为改变是非常重要的。     

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.     

Clinicopathological significance of stromal myofibroblasts in invasive ductal carcinoma of the breast.

The purpose of this study was to investigate the distribution of CD34-positive fibroblasts and alpha-smooth muscle actin (alpha-SMA)-reactive myofibroblasts in the stroma of benign and malignant breast lesions and, secondly, to determine whether the presence of stromal myofibroblasts is associated with some of the clinicopathological characteristics of patients with invasive ductal carcinoma. The presence of stromal CD34-positive fibroblasts and myofibroblasts was investigated (as defined immunohistochemically) in 8 normal breast tissue samples, 58 invasive ductal carcinomas, 9 ductal carcinomas in situ and 16 specimens with benign lesions of the breast (fibroadenomas, ductal hyperplasias). We further studied the correlations between the presence of stromal myofibroblasts with 7 clinicopathological parameters in 58 invasive ductal carcinomas. The results indicated that the stroma of normal breast tissues contained CD34-positive fibroblasts. All benign breast lesions exhibited stromal CD34-positive fibroblasts. In contrast, the stroma of ductal carcinomas showed a complete loss of CD34-positive fibroblasts. alpha-SMA expression in stromal fibroblasts (myofibroblasts) was not detected in normal tissue samples or benign lesions except in 1 case of fibroadenoma, whereas positive myofibroblasts were found in 44.4% of ductal carcinomas in situ and 56.9% of invasive breast carcinomas. Comparison of clinicopathological parameters between invasive ductal carcinomas with and without stromal myofibroblasts revealed significant differences in lymph node metastasis, high histological grade and high microvessel density. These results suggest that CD34 loss and the presence of myofibroblasts favor the diagnosis of breast carcinoma. In invasive ductal carcinoma, the presence of stromal myofibroblasts correlated significantly with pathological parameters associated with a poor prognosis.     

全数字化俯卧式X 线立体钢丝定位术在乳腺微钙化病灶中的应用价值*

目的:探讨X 线立体定位钢丝引导切取活检术（SWLB）对乳腺微钙化病灶的临床应用价值。方法:回顾性分析2007年5 月至2008年5 月南方医科大学附属深圳妇幼保健院45例行SWLB 活检的乳腺隐匿性病变,所有病例均为临床触诊阴性而乳腺X 线摄影发现微钙化病灶,将活检标本病理结果与X 线表现进行对照。结果:45例SWLB 活检组织标本病理结果中恶性病变13例（28.9%）,其中包括导管原位癌3 例（23.1%）,导管原位癌伴微浸润4例（30.8%）,浸润性导管癌5 例（38.5%）,导管内乳头状癌1 例（7.7%）;良性病变32例（71.1%）,其中包括导管上皮重度非典型增生2 例（6.3%）。 结论:SWLB 可准确引导切检临床阴性的乳腺微钙化病灶,明确乳腺微钙化的性质,提高早期乳腺癌的检出率。      

Expression of HIF-1α in breast cancer and precancerous lesions and the relationship to clinicopathological features简

Objective： The aim of this study was to observe the expressions and clinical significance of HIF-1a in breast cancer and precancerous lesions, and analyze the relationship between the expressions and clinicopathological features in breast cancer. Methods： We analyzed the HIF-1a expression in 128 cases of invasive ductal carcinomas, 146 precancerous lesions patients including 89 cases of ductal carcinoma in situ and 57 cases of atypical ductal hyperplasia. 53 cases of usual ductal hyperplasia breast tissues were selected as a control group. The specimens were evaluated for HIF-1a, estrogen receptor （ER） ＆ progesterone receptor （PR）, epidermal growth factor receptor type 2 （HER2/neu） and Ki-67. Immunoreactivity was semi-quantitatively evaluated in at least 1000 cells examined under the microscope at 40 x magnification and recorded as the percentage of positive tumor cells over the total number of cells examined in the same area. The percentage scores were subsequently categorized. The express of HIF-1a and their relationship with multiple biological parameters including ER ＆ PR, HER2/neu and Ki-67, the biomarkers levels of CA153, CA125 TSGF, and CEA in blood serum and nipple discharge, histological grade, region lymph node metastasis, distant metastasis and recurrence on files were also assessed. Results： Compared with usual ductal hyperplasia, the positive expression rate of HIF-1a in atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinomas group was significantly increased （P 〈 0.01）. The positive rates of HIF-1a in invasive ductal carcinomas were 68.75%, which were significantly higher than that in ductal carcinoma in situ （43.8%）, atypical ductal hyperplasia （31.6%）, usual ductal hyperplasia （9.4%; X2 = 13.44, 22.27, 52.79, respectively, P 〈 0.01）. Statistical analysis showed that difference of abnormal expression rate of HIF-1a between ductal carcinoma in situ and usual ductal hyperplasia （X2 = 18.37, P = 0.00）, atypical ductal hyperplasia and usual ductal hyperplasia （x2 = 8.14, P = 0.00） was significant （P = 0.00）. However, no significant difference in the positive expression rate of HIF-1a was found between atypical ductal hyperplasia and ductal carcinoma in situ tissue （X2 = 2.19, P = 0.14）. There was a significantly difference in the mean HIF-1a frequency between ER ＆ PR positive invasive ductal carcinomas group and negative group, epidermal growth factor receptor type 2 （HER2/neu） positive and negative groups, Ki-67 proliferation index 〈 14% and 〉 14% groups, histological grade （I ＋ II） and grade III invasive ductal carcinomas groups, with lymph node metastasis, distant metastasis and recurrence groups （P 〈 0.05） and without groups （P 〈 0.05）. However, there was not difference in the mean HIF-1a between age （〈 50 years vs 〉 50 years）, tumor diameter （〈 2 cm vs 〉 2 cm; P 〉 0.05）. The nipple discharge and serum levels of CA153, TSGF, CA125 and CEA in invasive ductal carcinomas HIF-1a positive patients were significantly higher than those in the negative patients （P 〈 0.05）. Conclusion： In breast cancer, HIF-1a expressibn was abnormally increased. The aberration of HIF-1a may play a key role during oncogenesis （atypical ductal hyperplasia or ductal carcinoma in situ） and promote breast cellular transformation into malignancy, a finding useful for further understanding of tumorigenesis. The abnormal expression of HIF-1a may be as an early event in the development of breast tumor. The over-expression of HIF-1a might be important biological markers for invasion, metastasis and recurrence of breast cancer.     

Nipple aspirate fluid cytology in breast carcinoma

BACKGROUND: Nipple aspirate fluid (NAF) cytology is a simple noninvasive method to study cells exfoliated into the ductal system of the breast. In the current study, the significance of cytologic findings in NAF was determined by correlating them with histopathologic findings from corresponding breast tissue. Cytologic-histologic correlations of NAF were performed in only a few studies. METHODS: Nipple aspirate fluid was collected by breast massaging and by using a breast aspiration device from 74 women with biopsy confirmed intraductal or invasive carcinoma with or without a history of preoperative neoadjuvant chemotherapy. Cytospin preparations were Pap stained. The number of epithelial cells was quantitated and foamy macrophages were semiquantitatively scored. Cytologic findings were categorized as insufficient for diagnosis (less than 10 epithelial cells), benign, mild atypia, marked atypia or suspicious, and malignant. Finally, they were correlated with tissue findings. RESULTS: Nipple aspirate fluid was obtained from 74 women, including 24 who had received preoperative neoadjuvant chemotherapy. The median age of patients was 54 years. A mean volume of 57 microL NAF and a mean of 149 epithelial cells were obtained. Foamy macrophages were present in 51 (70%) of the specimens. There was a significant correlation between the presence of epithelial cells and foamy macrophages (P < 0.001). Patients treated with chemotherapy had fewer epithelial cells in their NAF compared with patients who were not treated with chemotherapy. Thirty specimens (41%) were inadequate for diagnosis, 34 were (46%) benign, 5 (7%) were mildly atypical, 1 (1%) was markedly atypical, and 4 (5%) were malignant. Of the five cases with mildly atypical cytology, three were intraductal papilloma, one was low-grade papillary intraductal carcinoma, and one was low-grade intracystic papillary carcinoma with invasion in the corresponding tissue specimen. The single case with markedly atypical NAF cytology had extensive ductal carcinoma in situ (DCIS). Of the four cases with malignant NAF cytology, two were extensive DCIS and two had invasive carcinoma with extensive DCIS in the breast specimen. Overall, 3 (27%) of 11 cases of DCIS were detected in NAF and only 2 (4%) of 52 invasive carcinomas including the only two cases with extensive DCIS were detected in NAF. CONCLUSION: The probability of detecting malignant cells in NAF is dependent on the extent of DCIS and nipple involvement by DCIS. Nipple aspirate fluid is not a sensitive test for detecting invasive carcinoma of the breast. Atypical cytology in NAF is associated with papillary lesions in the underlying breast.     

bcl-2蛋白在良性乳腺病变及乳腺癌组织中的表达

目的　观察bcl-2蛋白在乳腺癌及良性乳腺病变中的表达。方法　采用免疫组化方法检测 15例正常乳腺组织、18例导管增生、10例不典型导管增生 ,10例小叶增生 ,6 9例浸润型乳腺癌和 45例乳腺导管原位癌中bcl -2蛋白表达。结果　bcl -2在 15例正常乳腺组织、18例导管增生、10例不典型导管增生及 10例小叶增生中均呈阳性 (10 0 % ) ,且均为高表达 ;bcl -2蛋白在 6 9例浸润型乳腺癌和 45例导管原位癌的表达阳性率分别为 6 5 2 % (45例 )和 75 6 % (3 4例 )。结论　bcl -2蛋白在正常乳腺组织良性乳腺病变的表达明显高于乳腺癌的表达。可能是在肿瘤的发展过程中bcl -2失去表达的结果 ,其原因和机理还有待进一步研究     

Expression of survivin, bcl-2, P53 and bax in breast carcinoma and ductal intraepithelial neoplasia (DIN 1a)

Survivin is a recently discovered member of the family of proteins that inhibits apoptosis. This anti-apoptotic compound can be detected in most types of cancer and expression is associated with a poor prognosis. We, immunohistochemically, investigated the expression of survivin in breast carcinomas and intraductal epithelial neoplasia of the breast to determine whether expression of this protein is associated with clinicopathological parameters such as grade, stage, mitotic rate. In 34 out of 43 cases (79.1%) of breast carcinoma and 22 out of 62 cases (35.4%) of intraductal epithelial neoplasia with mild, moderate and severe ductal epithelial, cell hyperplasia stained positively for survivin. None of the histological parameters analyzed were significantly correlated with survivin expression in breast carcinomas. In the carcinoma cases, survivin expression was positively correlated with expression of bcl-2, but was not correlated with expression of p53, bax, c-erbB-2 and estrogen, or progesterone. Some of the intraductal epithelial neoplasia cases with moderate or severe ductal epithelial hyperplasia stained positively for both survivin and p53. Breast carcinomas exhibited a significant expression of survivin, p53, and bcl-2 compared to breast with intraductal epithelial neoplasia. Survivin was not correlated with any of the clinicopathological parameters studied, however it could be a useful tool in early carcinomas and florid, severe ductal epithelial hyperplasia.     

伴多发性乳头状瘤的乳腺病变的临床病理分析

目的探讨乳腺病变中多发性头状瘤(MPS)与乳腺癌之间的关系.方法对20例伴有MPS的病变进行回顾性临床病理分析.所有的病例均有纤维囊性乳腺病、不典型性导管增生(ADH)、不典型性小叶增生(ALH)、小叶原位癌(LCIS)及不典型性乳头结构,与伴有MPS的导管原位癌(DCIS,8例)及导管侵袭癌(INS,12例)比较.结果乳腺MPS病变的特征性是在形成多发性肿块的导管内充满乳头,相邻的组织纤维化,伴有不同程度的增生性纤维囊性病.特别是在不典型性乳头状瘤病例(8例中5例,占62.5%)中,不典型增生常见(20例中9例,占44.1%).结论乳腺MPS往往与ADH、ALH、LCIS的恶性病变相关,而双侧乳腺MP提示乳腺癌发生的危险明显增加.     

Epithelial proliferative lesions and carcinomas in fibroadenomas of the breast

Sixteen cases of fibroadenomas with epithelial proliferative lesions (EP lesions) with histologic features resembling those of epithelial hyperplasia, sclerosing adenosis, and microglandular adenosis, and four cases of carcinomas in fibroadenomas (CA lesions) were studied histopathologically and immunohistochemically. The CA lesions included one intraductal carcinoma, two invasive ductal carcinomas, and one lobular carcinoma in situ. The histologic features of the EP lesions and CA lesions were fundamentally the same as those of carcinomas commonly observed in the mammary gland. Immunohistochemically, smooth muscle actin was useful in the detection of myoepithelial cells, particularly in EP lesions of the adenosis type (sclerosing adenosis or microglandular adenosis), and in distinguishing carcinoma. The differences between EP lesions and CA lesions of sites of immunoreactivity to CA15-3, CEA, and EMA were also helpful for differential diagnosis.     

Breast Lesion Excision System in the diagnosis and treatment of intraductal papillomas – A feasibility study

Objectives

This study aims to evaluate the feasibility of Breast Lesion Excision System (BLES) in the treatment of intraductal papillomas.

A comparison of the results of long-term follow-up for atypical intraductal hyperplasia and intraductal hyperplasia of the breast

Follow-up information was obtained on 199 women with breast biopsy specimens containing intraductal epithelial proliferation. The proliferations were divided into regular or ordinary intraductal hyperplasia (IDH) (117 cases) and atypical intraductal hyperplasia (AIDH) (82 cases). The average length of follow-up was 14 years for the patients with IDH and 12.4 years for the patients with AIDH. Of the 117 patients with ordinary IDH, carcinoma subsequently developed in six (5%); three of these were invasive carcinomas (2.6%). All three invasive carcinomas were in the ipsilateral breast, but of the three intraductal carcinomas (IDCa), two were in the contralateral breast. Of the 82 patients with AIDH, invasive carcinoma subsequently developed in eight (9.8%); six of these were located in the ipsilateral breast and two in the contralateral breast. One of these six patients died of disseminated carcinoma. The average interval to the subsequent carcinoma (intraductal and invasive carcinoma) was about the same in the two groups (8.3 years for AIDH and 8.8 years for IDH lacking atypia). When considering only subsequent invasive carcinomas, the interval was 8.3 years for the AIDH and 14.3 years for the IDH lacking atypia. Of the 14 patients with IDH and a family history of breast carcinoma, invasive carcinoma subsequently developed in one (7%) as compared with two (2%) of the 91 with a negative family history. Among patients with AIDH, invasive carcinoma subsequently developed in two of the 13 (15%) of those with a family history of breast carcinoma as compared with one of 57 (1.8%) of the women with a negative family history. The presence of atypia in epithelial hyperplasia is a significant factor in increasing the likelihood of the development of subsequent invasive carcinoma (P = 0.03; two-tailed test). Of women with AIDH, invasive carcinoma subsequently developed in 17% of those with sclerosing adenosis (SA) as compared with 4.2% of those without it. Therefore, SA may be a contributing factor to increased risk. A positive family history also appears to increase the likelihood of the subsequent development of invasive carcinoma, particularly in patients with AIDH.     

Prevalence of benign, atypical, and malignant breast lesions in populations at different risk for breast cancer. A forensic autopsy study

A forensic autopsy series of 519 women more than 14 years old was studied for prevalence of benign, atypical, and occult malignant breast lesions. The women included Anglos (non-Hispanic whites), Hispanics, and American Indians from New Mexico and Eastern Arizona. These three ethnic/racial groups are at markedly different risk for the development of breast cancer (Anglo 89 of 100,000 women per year, Hispanic 45.5, and American Indian 24.9. There were striking ethnic/racial and age-related differences in both the prevalence and magnitude of all forms of nonproliferative and proliferative fibrocystic disease. The various subsets of fibrocystic disease were highly associated with each other. Such lesions as apocrine metaplasia, sclerosing adenosis, and lobular microcalcification showed as much difference according to ethnic/racial background and age as the more common cystic change and duct epithelial hyperplasia. Atypical lobular and ductal hyperplasia, carcinoma in situ, and occult invasive carcinoma were uncommon and also occurred in ethnic/racial groups in a pattern that parallels the cancer risk in those groups.     

Possible Prognostic Role of HER2/Neu in Ductal Carcinoma In Situ and Atypical Ductal Proliferative Lesions of the Breast

HER2/neu is a well-established prognostic and predictive factor for invasive breast cancer. However, the role of HER2/neu in ductal breast carcinoma in situ (DCIS) is debated and recent data have suggested that it is mainly linked to in situ local recurrence. Although molecular data suggest that atypical ductal hyperplasia (ADH) and duct carcinoma in situ (DCIS) are related lesions, albeit with vastly different clinical implications, the role of HER2/neu expression in atypical ductal hyperplasia is not well de ned either. The aim of this study was to evaluate over expression of HER2/neu in DCIS and cases of ADH in comparison with invasive breast carcinoma. Archival primary breast carcinoma paraf n blocks (n15), DCIS only (n10) and ductal epithelial hyperplasia and other breast benign lesions (n25) were analyzed for HER2/neu immunoexpression. Follow up was available for 40% of the patients. HER2/neu was positive in 80%of both DCIS and invasive carcinoma, and 67% of atypical ductal hyperplasia (ADH) cases. Thus at least a subset of patients with preinvasive breast lesions were positive, which strongly suggests a role for Her2/neu in identifying high-risk patients for malignant transformation. Although these are preliminary data, which need further studies of gene ampli cation within these patients as well as a larger patient cohort with longer periods of follow up, they support the implementation of routine Her2/neu testing in patients diagnosed as pure DCIS and in orid ADH.     

Expression of tumor-associated antigen (DF3) in atypical hyperplasias and in situ carcinomas of the human breast

The monoclonal antibody (MoAb) DF3 prepared against a membrane-enriched fraction of human breast carcinoma has previously shown a differential reactivity to cytoplasmic antigen in carcinomas versus antigen concentrated on apical borders in benign lesions of the breast. In the present report the cytoplasmic reactivity of MoAb DF3 within a spectrum of benign and malignant breast lesions was studied to define whether the DF3 antigen is expressed in the cytoplasm of potentially premalignant lesions, i.e., atypical hyperplasias, or early malignant lesions, i.e., in situ carcinomas. Biopsy specimens of breast lesions from 108 women, including 28 patients with invasive carcinoma, 12 with in situ carcinoma, 17 with atypical hyperplasia, 25 with proliferative lesions without atypia, and 26 with nonproliferative lesions, were examined for DF3 antigen expression with the use of an indirect immunohistochemical method. Atypical hyperplasias were less reactive with MoAb DF3 than invasive carcinomas (P = .05 by Wilcoxon rank sum test). No significant statistical differences were observed, however, between invasive carcinomas and in situ carcinomas or between in situ carcinomas and atypical hyperplasias on the basis of cytoplasmic DF3 reactivity. Invasive carcinomas, in situ carcinomas, and atypical hyperplasias, however, demonstrated significantly higher reactivity with MoAb DF3 in the cytoplasm than proliferative lesions without atypia and nonproliferative lesions (P less than .01). These studies demonstrate that atypical hyperplasias express elevated levels of a given tumor-associated antigen and thus provide further immunologic evidence that these lesions are premalignant.     

乳腺导管内增生病变中p53表达与外显子突变的研究

目的：肿瘤抑制基因p53异常是浸润性乳腺癌发生发展中常见事件,而其与包括普通型增生（usualductal hyperplasia,UDH）、不典型增生（atypical ductal hyperplasia,ADH）及导管内原位癌（ductal carcinoma insitu,DCIS）的乳腺导管内增生性病变关系不明。本研究旨在探讨乳腺导管内增生性病变中p53外显子突变及突变型p53蛋白表达情况,以期了解p53突变及蛋白表达在乳腺癌发生发展中的作用。方法：用高分辨率熔解曲线（high-resolution melting,HRM）结合测序研究140例乳腺导管内增生性病变中p53外显子5-8的突变情况。用免疫组化研究240例乳腺导管内增生性病变中突变型p53蛋白表达情况。结果：经过HRM分析,共17例患者DNA熔解曲线与野生型标准品熔解曲线大于阈值结合测序分析结果发现,其中16例出现p53外显子突变。p53在UDH、ADH及DCIS中的突变率为0.0%（0/40）,12.7%（8/63）和21.6%（8/37）,三者间差异显著（P〈0.05）。40例UDH中未出现突变型p53蛋白阳性表达,在14.6%（19/130）的ADH出现阳性表达,在31.4%（22/70）的DCIS中出现阳性表达,三者间差异显著（P〈0.05）。Spearman相关性分析示突变型p53蛋白表达与p53外显子突变呈正相关（r=0.792,P〈0.01）。结论：p53外显子突变及突变型p53蛋白表达发生于乳腺导管内增生性病变中的ADH与DCIS,其可能为乳腺癌发生发展中的早期事件。