Comparison of estrogen receptor immunocytochemical assay in frozen and paraffin sections.

Frozen and paraffin sections of 11 breast carcinomas were stained for estrogen receptors (ER) using the same rat monoclonal primary antibody, D75P3, as the marker and alkaline phosphatase as the chromogen-linking enzyme. The results of this staining process were assessed visually and with the microTICAS image analysis system to determine the degree of correlation between frozen and paraffin-embedded tissue. In all specimens, some fraction of the nuclei stained positively. This included two specimens selected for their biochemically negative assay; one of them stained strongly positively with D75P3. The results of quantitative analysis support the visually apparent correlation between the two types of samples in terms of both overall staining pattern and intensity of nuclear staining. Although the conclusions of this pilot study are limited because of the small number of cases, this method of staining establishes the feasibility of representative ER determination in archival paraffin-processed material. The additional information provided by this method is potentially useful in stratifying patients in prospective studies on the basis of the efficacy of hormonal therapy in biochemically ER positive breast tumors.     

Quantitative image analysis of estrogen and progesterone receptors as a prognostic tool for selecting breast cancer patients for therapy

OBJECTIVE: To assess estrogen and progesterone receptor presence in human breast tumors using immunocytochemical analysis. STUDY DESIGN: For both estrogen (ER) and progesterone (PR) receptor assay, percent of stained cells and intensity of staining were estimated on a series of 251 consecutive breast cancer cases from the M. Ascoli Cancer Hospital Center in Palermo using the CAS 200 image analysis system. RESULTS: Cytochemical assay revealed a differential distribution of both ER and PR, by menopausal status of the patients; premenopause (PreM) was mostly ER negative (63%), and postmenopause (PostM) > 10 years was mostly ER and PR positive (64%). The percent of cells stained for ER was significantly different between PreM and PostM patients when they were considered as a whole. By contrast, no difference emerged for PR staining among menopausal groups. Overall, patients whose tumors were PR positive showed a significantly (P < .03) longer interval free of relapse. CONCLUSION: The present results suggest that PRs behave as better indicators than ERs of early relapse in breast cancer patients. Further studies, with longer follow-up, are needed, however, to validate this concept.     

Assessment of hormone receptors in breast carcinoma by immunocytochemistry and image analysis. II. Estrogen receptors

Frozen sections of 30 invasive breast carcinomas were stained for estrogen receptors (ERs) and the tumor cell proliferative rate by an immunoalkaline phosphatase technique. The stained sections were evaluated for ER by the microTICAS image analysis system. Seventeen tumors were ER positive and 13 were ER negative by image analysis. There was 93% concordance between the ER results obtained by image analysis and those obtained by biochemical methods. One case that was ER negative by image analysis was weakly positive by biochemical assay; a second case was ER positive by image analysis but ER negative by biochemical assay. Twelve of the 17 ER-positive tumors were diffusely positive while 5 displayed considerable intratumoral heterogeneity, with tumor cells exhibiting a broad range of intensity of receptor expression. In most cases, the image analysis ER status coincided with the progesterone receptor (PR) status, but in a large minority of cases (41%) the ER status and the PR status differed. Tumors with a high growth fraction (greater than 30%), as measured by Ki-67 immunostaining, were uniformly ER negative. The results of this investigation suggest that immunohistochemical staining of frozen sections for ER aided by automated image analysis (1) reliably detects the receptor in breast carcinoma, (2) allows for the assessment of heterogeneity within tumors and (3) may be used as part of a panel of antibodies to markers of potential prognostic importance in a single small tissue sample.     

Automated assessment of breast cancer margin in optical coherence tomography images via pretrained convolutional neural network

The benchmark method for the evaluation of breast cancers involves microscopic testing of a hematoxylin and eosin (H&E)‐stained tissue biopsy. Resurgery is required in 20% to 30% of cases because of incomplete excision of malignant tissues. Therefore, a more accurate method is required to detect the cancer margin to avoid the risk of recurrence. In the recent years, convolutional neural networks (CNNs) has achieved excellent performance in the field of medical images diagnosis. It automatically extracts the features from the images and classifies them. In the proposed study, we apply a pretrained Inception‐v3 CNN with reverse active learning for the classification of healthy and malignancy breast tissue using optical coherence tomography (OCT) images. This proposed method attained the sensitivity, specificity and accuracy is 90.2%, 91.7% and 90%, respectively, with testing datasets collected from 48 patients (22 normal fibro‐adipose tissue and 26 Invasive ductal carcinomas cancerous tissues). The trained network utilizes for the breast cancer margin assessment to predict the tumor with negative margins. Additionally, the network output is correlated with the corresponding histology image. Our results lay the foundation for the future that the proposed method can be used to perform automatic intraoperative identification of breast cancer margins in real‐time and to guide core needle biopsies.      

Prognostic evaluation of breast cancer in cytologic specimens

OBJECTIVE: To evaluate prognostic factors in breast cancer using cytologic samples and to determine the correlation between those factors and ploidy. STUDY DESIGN: Two hundred sixteen fine needle aspirates from patients with primary breast cancer were analyzed for expression of estrogen receptors (ERs), progesterone receptors (PRs), Ki-67 antigen, expression of p53 tumor suppressor gene and overexpression of c-erbB-2 using a standard immunochemical method. Not all subjects had all biomarker information because of the study design (c-erbB2 added later). The specimens were analyzed also for ploidy. We used the SAMBA 4000 image analysis system for quantification of the percent of cells stained positively by the different immunocytochemical stains andfor ploidy. RESULTS: A significant correlation wasfound between ER and PR and between Ki-67 and positive p53. Steroid receptor content was not significantly related to p53, Ki-67 or c-erbB2. No correlation was found between c-erbB2 and the other biomarkers. Ploidy had a significant correlation with all the biomarkers used. CONCLUSION: A reliable and rapid evaluation of markers for breast cancer can be achieved by measuring cells stained positively by immunocytochemical stains, as well as ploidy, by means of an image analysis system. ER, PR Ki-67, p53 and c-erbB2 had a significant correlation with ploidy and overall prognostic value in breast cancer.     

Computer-assisted immunocytochemical determination of breast cancer steroid receptors on cytological smears of excised surgical specimens compared with frozen sections

BACKGROUND: Due to the widespread use of fine needle aspirate biopsy the practice of determining estrogen (ER) and progesterone (PR) receptors in breast carcinoma from cytological smears (CS) is becoming very common. The aim of this study was to determine concordance between ER and PR assessed by immunocytochemical assay (ICA) on CS and FS both evaluated by image analysis since we have found no data in literature on this. METHODS: 104 breast carcinoma cases were selected. For all cases ER and PR determination was performed on CS, obtained by light scraping of the freshly cut surface of the excised surgical tumors at the time of frozen section diagnosis, and FS using the same monoclonal antibodies. Computer-assisted image analysis was performed in all cases using CAS 200. Results were expressed as percent positive area of neoplastic nuclei compared with total nuclear area of the examined neoplastic cells. RESULTS: Good correlation was demonstrated between percent positive nuclear neoplastic area by ER-ICA on CS and FS (r = 0.759; P < 0.0001). Concordance of results was 90.19% (P < 0.001). Good correlation was also demonstrated between percent positive nuclear neoplastic area by PR-ICA in CS and FS (r = 0.889; P < 0. 0001). Concordance of results was 97.02% (P < 0.0001). CONCLUSIONS: Our data suggest that ICA on CS with automated image analysis is efficient in evaluating ER and PR content in human breast cancer, especially when CS is the only method pathologists have to evaluate receptor status e.g. in advanced breast cancer cases when neoadjuvant therapy is necessary before surgery or when surgery is impossible.     

Quantitation of the immunocytochemical assay for estrogen receptor protein (ER-ICA) in human breast cancer by television imaging

A Quantimet 720D Image Analysis System has been programmed for light microscopic evaluation of the nuclear estrogen receptor distribution in frozen sections of human breast cancer stained by the peroxidase-antiperoxidase method using monoclonal antibodies to estrogen receptor protein (ER). This method provides precise criteria for distinguishing ER-positive and -negative cells and a sensitive and reproducible means for densitometric quantification of the staining patterns. Although imaging sequence and graphic analysis are automated by computer programs, light pen interaction provides supervision of feature selection. Imaging of the immunocytochemical assay (ER-ICA) in 50 patients revealed marked heterogeneity of nuclear estrogen receptor concentration varying over a nearly 100 fold concentration range. Various ER concentration patterns were evident: (I) distributions with a single peak (CV = 5%) present at various concentration levels; (II) bimodal distributions, revealing co-existent ER-positive and ER-negative subpopulations; (III) multimodal distributions with a number of resolvable concentration peaks; and (IV) highly skewed distributions with or without discernible peaks, frequently extending over the entire concentration range. Statistical methods of de-convolution were applied to determine the frequency and ER concentration characteristics of component subpopulations in the mosaic cases and for resolving the proportion of ER-positive and -negative cells. An approach for evaluating nuclear ER content in conjunction with ER concentration patterns in individual patients revealed whether spread in the ER concentration distribution resulted from differences in nuclear ER content or from variability in nuclear volume distribution.     

Spectrally Resolved Morphometry of the Nucleus in Hepatocytes Stained by Four Histological Methods

A novel concept of spectrally resolved morphometry for histological specimens was developed using light microscopy combined with spectrally resolved imaging. The spectroscopic characteristics of rat hepatocytes stained by Haematoxylin and Eosin, Romanowsky–Giemsa, periodic acid–Schiff and Masson's trichrome were assessed. Light intensity in the range 450–850 nm was recorded from 10000 pixels of nuclear domains of each stained cell and represented as light transmittance spectra and optical density. In order to identify spectral shifts caused by stain– macromolecule interactions, we compared the spectra of individual stain components with those of DNA and bovine serum albumin. Chromatin and interchromatin areas were classified spectrally using a chosen spectral library followed by morphometric calculations of nuclear domains for each staining method. The spectral fingerprints of Masson's trichrome stain distinguished the nucleolus from the rest of the nuclear c hromatin, enabling the demarcation and calculation of the nucleolar area. Spectrally resolved imaging of human hepatocytes stained by Masson's trichrome stain revealed marked differences between the nucleolar area in normal human hepatocytes compared with hepatocellular carcinoma. Masson's trichrome stain also distinguished the nucleolar area in human breast carcinoma cells and keratinocytes.     

Fine needle aspirate cell blocks are reliable for detection of hormone receptors and HER‐2 by immunohistochemistry in breast carcinoma

S. P. Bueno Angela, R. M. Viero and C. T. Soares Fine needle aspirate cell blocks are reliable for detection of hormone receptors and HER‐2 by immunohistochemistry in breast carcinoma Aims: To evaluate the reliability of fine needle aspirate cell blocks in the assessment of oestrogen receptor (ER), progesterone receptor (PR) and HER‐2/neu proteins by immunohistochemistry in comparison with surgical specimens. Materials and methods: This is a retrospective study of 62 cases of breast carcinoma diagnosed by fine needle aspiration cytology (FNAC) and confirmed using the surgical specimen. Immunohistochemical tests were performed to assess the presence of oestrogen receptor (ER), progesterone receptor (PR) and HER‐2/neu proteins in cell blocks and the corresponding surgical specimens. The cell block method used alcohol prior to formalin fixation. Cases with 10% or more stained cells were considered positive for ER and PR. Positivity for HER‐2/neu was assessed on a scale of 0–3+. The criterion for positivity was a score of 3+. Results: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of the cell blocks in the investigation of ER, PR and HER‐2/neu protein (3+) were (%): ER, 92.7, 85.7, 92.7, 85.7 and 90.3; PR, 92.7, 94.7, 97.4, 87.0 and 93.5; HER‐2/neu, 70.0, 100.0, 100.0, 94.5 and 95.2. Discrepancies were seen in cell blocks in the 1+ and 2+ HER‐2/neu staining scores: two of 12 cases scoring 2+ and one case of 26 scoring 1+ on cell blocks scored 3+ on surgical specimens. The correlation index between cell block and corresponding surgical specimen varied from 90% to 94%. Conclusion: Cell blocks provide a useful method of assessing ER, PR and HER‐2/neu, mainly for inoperable and recurrent cases, but consideration should be given to carrying out FISH analysis on 1+ as well as 2+ HER‐2/neu results.     

Measuring microvascular density in tumors by digital dissection

OBJECTIVE: To develop and validate a digital dissection techniquefor measuring the cross-sectional area of blood vessels in histologic sections of tumors routinely stained with hematoxylin and eosin. STUDY DESIGN: The procedure was first validated in four experimental tumors in rats by comparing the results of the digital dissection technique to functional estimates of the blood volume in the tumors as measured by dynamic, contrast-enhanced magnetic resonance imaging. The method was then tested on a variety of experimental and human tumors. RESULTS: The digital dissection technique yielded results that exactly matched the functional measurements of blood volume infour experimental tumors. Digital dissection of 40 additional tumors in rats showed that 21 infiltrating ductal carcinomas had significantly greater microvascular density (MVD) than 19 benign fibroadenomas (12% vs. 7.9%, P=.028 by two-tailed t test). In 10 human breast carcinomas the MVD was consistently greater than the measurement of blood vessel density as identified by immunohistochemical staining for factor VIII. The between-run coefficients of variation for the MVD assay were 12% (n = 5) for a human breast cancer and 18% (n = 5)for an experimental rat tumor. CONCLUSION: The digital dissection technique is a reproducible, objective and accurate method of measuring MVD in sections of tumors that are routinely stained with hematoxylin and eosin.     

Automatic image segmentation of nuclear stained breast tissue sections using color active contour model and an improved watershed method

Automatic image segmentation of immunohistologically stained breast tissue sections helps pathologists to discover the cancer disease earlier. The detection of the real number of cancer nuclei in the image is a very tedious and time consuming task. Segmentation of cancer nuclei, especially touching nuclei, presents many difficulties to separate them by traditional segmentation algorithms. This paper presents a new automatic scheme to perform both classification of breast stained nuclei and segmentation of touching nuclei in order to get the total number of cancer nuclei in each class. Firstly, a modified geometric active contour model is used for multiple contour detection of positive and negative nuclear staining in the microscopic image. Secondly, a touching nuclei method based on watershed algorithm and concave vertex graph is proposed to perform accurate quantification of the different stains. Finally, benign nuclei are identified by their morphological features and they are removed automatically from the segmented image for positive cancer nuclei assessment. The proposed classification and segmentation schemes are tested on two datasets of breast cancer cell images containing different level of malignancy. The experimental results show the superiority of the proposed methods when compared with other existing classification and segmentation methods. On the complete image database, the segmentation accuracy in term of cancer nuclei number is over than 97%, reaching an improvement of 3–4% over earlier methods.     

Estrogen receptor determination in fine needle aspirates of the breast. Correlation with histologic grade and comparison with biochemical analysis

Material obtained by fine needle aspiration (FNA) of 25 surgically removed breast carcinomas was tested for the immunocytochemical localization of estrogen receptor (ER) using the peroxidase-antiperoxidase method and a monoclonal antibody developed against human breast cancer ER. The results were compared to those obtained by the conventional biochemical analysis of cytosol protein. A semiquantitative relationship between the immunoperoxidase stain and the biochemical analysis suggests that cases in which greater than 70% of the cells stain and in which intense staining is present are likely to contain ER in a concentration of greater than 250 fmol/mg of cytosol. Less than 15% stained cells and an absence of intense staining is indicative of a concentration of less than 10 fmol/mg. In only one case was there a significant difference in positivity between the two methods, possibly as a result of a functional heterogeneity of the tumor cell population. Intense staining is strongly suggestive of a tumor of low histologic grade and was never seen in tumors with a high histologic grade or nuclear grade. The immunoperoxidase method of ER detection on material obtained by FNA is a semiquantitative means of selecting patients with breast cancer who are likely to respond to hormonal therapy. The method overcomes many important disadvantages of cytosol analysis and provides clinically significant information regarding the ER content and the degree of tumor differentiation.     

Cascade pattern recognition structure for improving quantitative assessment of estrogen receptor status in breast tissue carcinomas

OBJECTIVE: To develop and validate a computer-based approach for the quantitative assessment of estrogen receptor (ER) status in breast tissue specimens for breast cancer management. STUDY DESIGN: Microscopy images of 32 immunohistochemically (IHC) stained specimens of breast cancer biopsies were digitized and were primarily assessed for ER status (percentage of positively stained nuclei) by a histopathologist. A pattern recognition system was designed for automatically assessing the ER status of the IHC-stained specimens. Nuclei were automatically segmented from background by a pixel-based unsupervised clustering algorithm and were characterized as positively stained or unstained by a supervised classification algorithm. This cascade structure boosted the system's classification accuracy. RESULTS: System performance in correctly characterizing the nuclei was 95.48%. When specifying each case's ER status, system performance was statistically not significantly different to the physician's assessment (p = 0.13); when ranking each case to a particular 5-scale ER-scoring system (giving the chance of response to endocrine treatment), the system's score and the physician's score were in agreement in 29 of 32 cases. CONCLUSION: The need for reliable and operator independent ER-status estimation procedures may be served by the design of efficient pattern recognition systems to be employed as support opinion tools in clinical practice.     

Slide‐free imaging of hematoxylin‐eosin stained whole‐mount tissues using combined third‐harmonic generation and three‐photon fluorescence microscopy

Intraoperative margin assessment of surgical tissues during cancer surgery is clinically important, especially in the case of tissue conserving surgery like Mohs micrographic surgery in which minimization of the surgical area is considered crucial. Frozen pathology is the gold standard of assessing excised tissues for signs of remaining cancerous lesions. The current protocol, however, is time‐consuming and labor‐intensive. Instead of the complex frozen sectioning, staining, and traditional white light microscopy imaging protocol, optically sectioned histopathological imaging of hematoxylin‐eosin stained whole‐mount skin tissues with a subfemtoliter resolution is demonstrated by using nonlinear microscopy in this study. With our proposed method, the reagents of staining and the contrast of imaging are fully consistent with the current clinical standard of frozen pathology, thus facilitating rapid intraoperative assessment of surgical tissues for future applications. Image: Slide‐free nonlinear microscopy imaging of H&E stained whole‐mount skin tissue showing the morphology of sweat glands.      

Alterations of estrogen receptors, progesterone receptors and c-erbB2 oncogene protein expression in ductal carcinomas of the breast

Estrogens are important for stimulating the growth of a large proportion of breast cancers. Progesterone plays critical roles in breast development and tumorigenesis. The c-erbB2 gene (HER-2/neu) is a proto-oncogene expressed in 10-34% of breast cancers. Its expression is associated with poor clinical outcome. The hypothesis that the progression of in situ ductal carcinoma of breast to invasive ductal carcinoma is associated with alterations of ER, PgR and HER-2/neu protein expression was tested. Of 100 mastectomy specimens examined, all contained both ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDC) not otherwise specified (NOS). The status of ER, PgR and HER-2/neu proteins was examined by immunochemistry. ER and PgR protein expression was scored as the mean value of positively stained cells. HER-2/neu protein expression was evaluated on ts staining pattern (0, 1+, 2+ and 3+). We found variations between DCIS and IDC with significant decrease of the mean values of ER and PgR positively stained cells in high-grade (Grade 3) IDC (ER: 49.2+/-10.3 vs. 30.8+/-5.5 and PgR: 40.0+/-10.0 vs. 22.3+/-5.1 in DCIS and IDC, respectively, P<0.05). Invasive carcinomas with lymph node metastases or lymphovascular invasion or both had lower mean values of ER and PgR positively stained cells compared to those without these features. In IDC (Grade 3), HER-2/neu protein expression values (1.2+/-0.2) were significantly high compared to DCIS (0.7+/-0.3, P<0.05). In addition, HER-2/neu protein expression values were significantly higher (P<0.05) in IDC with lymph node metastases or lymphovascular invasion (1.5+/-0.3) than those without these features (0.8+/-0.2). A significantly high mean (P<0.05) of ER and PgR positively stained cells was observed in postmenopausal females compared to premenopausal women. In contrast, high HER-2/neu expression values were seen only in premenopausal females. A significant positive correlation was observed between ER and PgR receptor expression (r=0.81). A low degree inverse correlation (r=-0.24, P<0.012) was found between ER+/PgR+ tumors and HER-2/neu expression. These findings substantiate the notion that breast cancer progression is often associated with alterations of ER, PgR and HER-2/neu expression. The underlying mechanisms of these alterations are open for further investigation.     

Technique and feasibility of a dual staining method for estrogen receptors and AgNORs.

A new staining method for dual demonstration of Estrogen receptors (ER) and argyrophilc Nucleolus-Organizer Regions (AgNORs) was developed. To rule out possible reciprocal effects, serial slides of 10 invasive ductale breast cancers were stained with either the single staining method or the simultaneous ER/AgNOR-staining method and investigated comparatively. By measuring the slides with the image analysis system AMBA, reciprocal effects could be excluded. It was proven that dual staining of both markers results in a reproducible and specific staining result. We concluded that it is justified to measure AgNORs in immunohistochemically stained cells.     

Different proliferation patterns in breast cancer: AgNOR measurements in ER-negative and ER-positive tumor cells.

The relation between estrogen receptors (ER) and argyrophilic nucleolar organizer regions (AgNORs) in situ within human breast cancer cells was analyzed. For AgNOR measurements in 49 invasive breast carcinomas, a new reproducible staining method for dual demonstration of ER and AgNORs was applied. Quantitative AgNOR variables were determined in ER-positive and ER-negative tumor cells by digital image analysis. The relationships between AgNOR parameters of ER-positive and ER-negative cells and other prognostic factors of breast cancer [Bloom-Richardson-Grading and growth fraction (Ki-67 index)] were investigated. A higher AgNOR content in ER-negative cells and a special clustering phenomenon in ER-positive tumor cells were found. Correlation with other criteria of malignant potential could be exclusively demonstrated for ER-negative cells. ER-negative cells of breast cancer can be characterized as the more malignant and possibly prognosis-dictating cell fraction. Thus, ER-negative cells probably contribute more to the progression of the tumor disease and furthermore to the prognosis than ER-positive cells. We recommend measurement AgNORs exclusively in ER-negative cells of breast cancer.     

Direct detection of herceptin/trastuzumab binding on breast tissue sections.

The protooncogene product HER-2/neu is the target of the humanized monoclonal antibody trastuzumab (Herceptin). Several tests are used clinically to identify patients with HER-2/neu overexpression based on evaluation by pathologists of gene amplification by fluorescence in situ hybridization or protein expression using immunohistochemistry (IHC). A simple technique has been developed for staining formalin-fixed, paraffin-embedded breast cancer tissue using unmodified Herceptin/trastuzumab as the primary antibody. Results were compared with staining with the commercial kit, HercepTest, as well as with polyclonal anti-HER-2/neu antibodies and with biotinylated trastuzumab. These procedures were tested using four breast cancer microarrays. There were 854 cores that were stained with all four antibodies, representing 325 cases. A standard 4-point scoring system (0-3) was used. A total of 156 cases (48%) were scored as 0 by all the methods used and 31 (9.5%) were positive (3+) by all methods. Of interest, three cases scored negative using polyclonal anti-HER-2/neu antibodies but were positive using unmodified trastuzumab. To clarify this discrepancy, whole sections of tumors were examined with both antibodies using double labeling. There were some tumors that demonstrated a mosaic pattern of staining with neighboring cells or groups of cells stained exclusively with one antibody or the other. These results demonstrate that unmodified humanized or human therapeutic antibodies could be used for preclinical testing or in a clinical laboratory setting for IHC-based selection of patients for treatment, and results of such selection could be different from those obtained using polyclonal antibody-based IHC procedure.     

乳腺癌超声征象与ER、PR、连环蛋白p120、癌基因CerbB-2、原癌基因Her-2/neu表达的关系研究

目的:探讨乳腺癌超声征象与雌激素受体(ER)、孕激素受体(PR)、连环蛋白p120、癌基因CerbB-2、原癌基因Her-2/neu表达的关系。方法:将2014年10月至2017年10月我院收治的50例乳腺癌患者纳入本研究,术前获得患者完整乳腺超声图像资料,术后通过免疫组织化学法检测ER、PR、CerbB-2、Her-2/neu和p120的表达情况。记录超声检查与组织标本检测结果,比较不同乳腺癌超声征象中ER、PR、CerbB-2、Her-2/neu和p120的表达情况。结果:p120阴性表达率为62.00%,ER阳性表达率为50.00%,PR阳性表达率为36.00%,CerbB-2阳性表达率为74.00%,Her-2/neu阳性表达率为30.00%。病灶边缘有毛刺征、周边有高回声晕征、无淋巴结转移患者的ER阳性表达率高于病灶边缘无毛刺征、周边无高回声晕征、淋巴结转移者(P0.05);病灶边缘有毛刺征、周边有高回声晕征患者的PR阳性表达率高于病灶边缘无毛刺征、周边无高回声晕征者(P0.05);内部有微小钙化、血流显像分级2-3级、淋巴结转移患者的p120阴性表达率高于内部无微小钙化、血流显像分级0-1级、无淋巴结转移者(P0.05);内部有微小钙化、血流显像分级2-3级、淋巴结转移患者的CerbB-2阳性表达率高于内部无微小钙化、血流显像分级0-1级、无淋巴结转移者(P0.05);内部有微小钙化、淋巴结转移患者的Her-2/neu阳性表达率高于内部无微小钙化、无淋巴结转移者(P0.05)。结论:乳腺癌超声征象与ER、PR、CerbB-2、Her-2/neu和p120的表达有紧密联系,可为治疗方案拟定提供参考。     

Expression of oestrogen receptor-beta in invasive breast tumours

Steroid hormone receptors are used routinely to predict endocrine responsiveness in patients with breast cancer. Two oestrogen receptors (ERs): ER alpha and ER beta have been identified. Although ER alpha and ER beta genes share a large degree of homology, it is generally thought that their distribution and function are substantially different in many tissues. Both of them may be expressed in normal and neoplastic tissues of the breast. While much is known about ER alpha, the role of ER beta is still undefined, especially at the protein level. Recent development of reliable antibodies to ER beta has provided opportunity to test immunohistochemical reactions detecting ER beta in archival breast tumours. The aim of our study was to learn more about the cellular mechanisms underlying the relationship of ER beta and progesterone receptor (PR) in breast cancer tissues, discriminating between hormone-dependent and hormone-independent tumours. ER alpha and PR content of tumour tissues of 154 patients with breast cancer were tested by in situ indirect immunohistochemical method parallel with ligand binding biochemical assay. ER beta was detected in 8 ER alpha-/PR+ breast carcinomas by immunohistochemical method too. Steroid hormone receptor content was analysed comparing to the histologic type and grading of the tumours. CONCLUSIONS: A considerable part of breast carcinomas belongs to the ER+/PR+ and ER-/PR- groups. About 1-2% of the tumours is expected to be ER alpha-/ER beta+/PR+ type. In such cases ER alpha negative reaction together with PR positivity can signal the necessity of the immunohistochemical detection of ER beta in routine histopathological practice, presenting the precise steroid hormone receptor status for the most effective endocrine therapy of the patients.