Prognostic significance of p53, bcl-2 and EGFR in carcinoma of the endometrium

OBJECTIVE: To evaluate the part played by several parameters in the prognosis of patients with endometrial carcinoma. STUDY DESIGN: Eighty imprint smears from fresh endometrial tumor specimens were studied immunocytochemically for the expression of p53, bcl-2 and epidermal growth factor receptor. Also, the presence of estrogen receptor (ER) and progesterone receptor (PR) in the tumor tissue was measured. The data obtained were related to survival, and associations were sought between the parameters studied. RESULTS: Strong associations were found between advanced stage, high grade, lymph node metastases at diagnosis, nonendometrioid histology and p53 expression with poor survival. Bcl-2 expression was associated with good five-year survival. ER expression was associated marginally with good five-year survival, but PR expression was not. A strong association was found between p53 and advanced disease, stage and lymph node metastases at diagnosis. An association between EGFR positivity and survival was not found. CONCLUSION: p53 Expression of uterine tumors is an independent and strong indicator of poor prognosis. Even patients with stage I and II disease at surgery who have p53-positive tumors must be considered at high risk.     

Age-associated biomarker profiles of human breast cancer

To explore the hypothesis that aging not only increases breast cancer incidence but also alters breast cancer biology, we correlated patient age and diagnosis with tumor histology, stage and biomarkers independently determined from two different tumor archives: an American collection of approximately 800 paraffin-embedded and immunohistochemically analyzed primary breast cancers, and an European collection of approximately 3000 cryobanked primary breast cancers analyzed by ligand-binding and enzyme immunoassay (EIA). The prognostic biomarkers chosen for comparison represented surrogate measures of tumor: (i). proliferation, growth and genetic instability (mitotic and apoptotic indices, Ki-67/MIB-1-positivity, nuclear grade, p53-positivity), (ii). endocrine-dependence (estrogen receptor (ER), progesterone receptors (PR), pS2, Bcl2), (iii). growth factor receptor-dependence (ErbB2, EGFR/ErbB1), and (iv). angiogenic, invasive and proteolytic potential (uPA, PAI-1, Cathepsin D, VEGF). No biomarker reflecting tumor angiogenic, invasive or proteolytic potential showed a significant correlation with patient age at diagnosis. In contrast, significant inverse correlations (|r|>0.1; P< or =0.05) were observed for all measures of tumor growth and genetic instability as well as growth factor receptor overexpression (ErbB2 or EGFR positivity). Only one marker of endocrine-dependence, ER expression, showed a significant positive correlation with patient age at diagnosis. In summary, these findings support the hypothesis that breast cancer biology is significantly affected by patient age. In particular, breast tumors arising in older patients have slower growth rates, are more likely to be ER-positive, and are less likely to be p53-positive, EGFR-positive or ErbB2-positive.     

Prognostic factors affecting disease-free survival rate following surgical resection of primary breast cancer.

In order to identify the prognostic factors that significantly influence the disease-free survival rate after surgical resection of primary breast cancers, we determined tumour and lymph node grades, and immunohistochemical staining for estrogen and progesterone receptors (ER and PR), c-erbB-2, p53, bcl-2, bax and PCNA in 76 patients. Univariate analysis showed that increased grade of tumour and lymph nodes, negative immunostaining for ER, positive immunostaining for c-erbB-2, and a high PCNA index (> or = 30%) negatively influenced the disease-free survival rate, but PR, p53, bcl-2 and bax had no predictive value. Although p53 was not an independent prognostic factor by itself, the combination of p53, bcl-2, and bax proved to correlate with the disease-free survival, with the best prognosis noted in tumours negative for p53 and positive for both bcl-2 and bax, intermediate prognosis in tumours negative for p53 and positive for either bcl-2 or bax and worst prognosis in tumors negative for p53 as well as bcl-2 and bax. Tumour grade correlated positively with PCNA index, while positive staining for ER correlated negatively with tumour grade as well as with PCNA index, although this was statistically insignificant. Immunostaining of breast cancers for bcl-2 correlated negatively with tumour grade and PCNA index. Immunostaining for c-erbB-2 correlated positively with PCNA but not with tumour grade. Immunostaining for p53 tended to correlate positively with PCNA, but not with tumour grade. Immunostaining for PR and bax did not correlate with tumour grade and PCNA index. These results suggest that in addition to tumour size and lymph node involvement, immunostaining for ER, c-erbB-2, and a high PCNA index are important prognostic factors in human breast cancer. Wild-type p53 with preserved bcl-2 and bax gene products is also a favorable prognostic factor indicating breast cancer at an early stage of cancer progression.     

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。     

Cytologic diagnosis of estrogen and progesterone receptors in breast imprints

OBJECTIVE: To investigate estrogen receptor (ER) and progesterone receptor (PR) levels in imprint specimens obtained at breast surgery and to compare their correlation with that of standard methods. STUDY DESIGN: Imprint specimens for cytology were obtained from 101 mass-forming lesions in 66 patients, and specimens were frozen in liquid nitrogen for later assay. The imprint specimens were immunocytochemically (ICC) stained by monoclonal antibody to ER or PR; diaminobenzidine-stained cell nuclei in clusters were regarded as positive. Tissue specimens were assayed by the standard method of dextran-coated charcoal assay (DCC) and enzyme immunoassay. RESULTS: Forty-five primary breast cancer lesions, 2 contralateral breast cancer, 49 dissected nodes and 5 benign breast lesions were collected. The correlation between DCC and ICC was 81% (82/101) for ER and 74% (66/101) for PR. That between EIA and ICC was 88% (88/99) for ER and 80% (79/100) for PR, higher than that between DCC and ICC for ER and PR. CONCLUSION: ICC assessment of ER or PR on imprint cytology is a promising clinical test with an acceptable correlation.     

Reduced clinicopathological influence of hormone-dependence on breast carcinomas in women older than 70 years

In order to evaluate the influence of hormone dependence on the features of infiltrating ductal carcinoma of the breast we have assayed the cytosolic levels of estrogen receptor (ER), progesterone receptor (PR), pS2 and cathepsin D in 53 women aged over 70 years and in 95 women aged between 55 and 70 years. Tumor size, axillary involvement, distant metastasis, histological grade, ploidy and S-phase were taken into account. Carcinomas of women aged over 70 did not show higher concentrations or higher positive results for ER and PR than those of women in the 55-70-year age group. In older patients, negativity for ER was associated only with higher S-phase fraction, while negativity for PR was not associated with any of the parameters analyzed. In the younger subgroup, negativity for ER was associated with larger tumor size, higher S-phase fraction, lymph node involvement, histological grade 3 and lower pS2 values. Negativity for PR was associated with the same parameters, as well as with a higher frequency of recurrence. Our results suggest a reduced influence of hormone dependence on the clinicopathological features of breast carcinomas in patients older than 70 years compared with women aged between 55 and 70 years.     

Fibrin sealant does not decrease seroma output or time to drain removal following inguino-femoral lymph node dissection in melanoma patients: A randomized controlled trial (NCT00506311)

Background

Breast carcinoma is a disease with a tremendous heterogeneity in its clinical behavior. Newer prognostic factors and predictors of response to therapy are needed. The aim of this study was to evaluate the expression of HER-2, estrogen receptor (ER) and progesterone receptors (PR) in breast carcinoma and to compare it with other prognostic parameters such as histological type and grade, tumor size, patients' age, and lymph node metastases.

Patients and methods

This is a retrospective study conducted in the department of pathology at Sfax University Hospital. Confirmed 155 Cases of breast carcinoma were reviewed in the period between January 2000 and December 2004. We used immunohistochemistry to evaluate the expression of HER-2, ER, and PR receptor and Chi-square and Fisher exact test to correlate immunohistochemical findings with prognostic parameters for breast carcinoma such as patients' age, tumor size, histological type, histological grade and lymph node status.

Results

The mean age of patients was 51.5 years, ranging from 22 to 89 years. 80 (51.6%) of the patients were below 50 years. The percentage of expression of HER-2, ER and PR was 26, 59.4, and 52.3%, respectively. HER-2 was over-expressed (3+) in 18.1% of the cases, was inversely related to ER expression (p = 0.00) and to PR expression (p = 0.048). This over-expression was also associated with a high tumor grade with marginal significance (p = 0.072). A negative correlation was noted between ER and PR expression and SBR grade (p = 0.000) and ER and age (p = 0.002).

Conclusion

HER-2 over-expression was observed in 18.1% of Tunisian breast carcinoma affecting female patients. This group presents apparently an aggressive form of breast carcinoma with high histological grade and negative ER.     

Women with large breasts are at an increased risk of advanced breast cancer

Background

The risk of nodal metastasis is higher in women with bigger breast. It is not clear if this increase is due to the size of the breast (largely related to obesity) or is the result of larger tumour size at presentation (due to delayed diagnosis). It is hypothesised that women with large breasts are more likely to have node positive disease mainly attributable to their breast size.

Patients and methods

One hundred and twenty consecutive patients who underwent mastectomy during the year 2004 and 2005 for primary breast cancers in a large Teaching Hospital were included in the study. Patient's variable and tumour variable were collected and analysed by SPSS^® computer programme.

Results

It was found that big breasted women (those patients with mastectomy weight greater than 800 g) had a significantly greater tumour size than those with smaller breasts (p = 0.019, Mann-Whitney test) but there was no significant difference in grade (Kendall's tau-b = 0.055, p = 0.57) or lymph node positivity (Kendall's tau-b = 0.011, p = 0.93) between the two groups. Although, the tumour size was significantly greater in those with lymph node metastases (p < 0.001) but mastectomy weight was not found to be significantly greater in those with lymph node metastases (p = 0.11). For patients with similar tumour sizes mastectomy weight was not significantly greater in those patients with lymph node metastases (p = 0.28).

Conclusion

It is concluded that increased incidence of lymph node positivity at presentation big-breasted women is because of larger size of the primary tumour and not due to the size of the breast alone.

     

Immunocytochemistry on scrape cytology in breast cancer: will it unearth the weaker positives?

OBJECTIVE: To standardize the technique of immunocytochemical (ICC) assessment of estrogen (ER) and progesterone receptor (PR) status in breast cancer by scrape cytology and to compare the results with immunohistochemistry on paraffin blocks. STUDY DESIGN: ICC assessment for ER and PR was done on scrape smears from tissue samples in 200 cases of primary breast cancer. The results were compared to those obtained from immunohistochemical (IHC) evaluation of formalin-fixed paraffin same tissue samples. RESULTS: ER/PR positivity rates as well as staining scores were compared between the scrape smears and tissue sections. The concordance between cytology and histology was 84% for ER and 90% for PR. Both the positivity rates and the staining intensity scores were higher for cytochemistry than for histochemistry. CONCLUSION: The ICC method on scrape smears is a simple test with rapid turnaround time. The sample required is small, and antigen loss due to fixation and processing is minimal. This new method gives a higher yield of hormone receptor positivity and, when used in conjunction with the IHC method, may improve the pickup rate of ER-positive cases, thereby playing an important role in risk stratification and therapeutic decision making in patients with breast cancer.     

Immunocytochemical versus biochemical receptor determination in normal and tumorous tissues of the female reproductive tract and the breast

The development of highly specific and sensitive monoclonal antibodies directed against human estrogen (ER) and progesterone receptors (PR) provides a new approach in precise histochemical receptor location independent of hormone binding. Over the years receptor determination was the domain of the radioligand-binding assay, in which receptors are measured by tritiated ligand and unbound ligand is removed by the dextran-coated charcoal (DCC) procedure. Presented here are the results and experiences obtained by the classic DCC and the immunocytochemical method in the different normal and tumorous tissues of the female reproductive tract and the breast. The results of both methods were compared, and overall concordance of the results was found to vary considerably among the different types of tissue analyzed. Best agreement (86%) was found for PR determination in breast cancer, and the lowest rate of concordance for ER determination in fibrocystic disease of the breast. Special attention was directed toward the heterogeneity of receptor distribution in the specimens examined. In all tissues investigated, ER and PR were located in the nuclei of cells in both paraffin and frozen sections. Staining intensity varied among different cell types and from cell to cell for a single cell type, as well as in tumorous and normal tissues. In breast cancer, randomly scattered single cell receptor positivity was distinguished from focal/clonal positivity. Paraffin-embedded lymph node metastases showed significantly weaker staining as compared with their respective primary tumors. In the normal ovary, the corpus luteum and the stromal layer of the outer cortex were revealed as highly receptive elements for progestins, whereas ER was barely demonstrable in the normal ovary. Benign serous and mucinous ovarian tumors showed opposite ER and PR distribution among the stromal and epithelial components. Of special interest were the highly significant changes in ER and PR content in the stromal and glandular cells of the different layers of the normal endometrium throughout the menstrual cycle.     

The assessment of multiple variables on breast carcinoma fine needle aspiration (FNA) cytology specimens: method, preliminary results and prognostic associations

The assessment of multiple variables on breast carcinoma fine needle aspiration (FNA) cytology specimens: method, preliminary results and prognostic associations
We have assessed multiple biological variables on breast carcinoma FNA specimens using a Cytoblock technique. The growth fraction (MIBI), oestrogen receptor (ER), progesterone receptor (PR), p53 mutant protein, c-erbB-2, epidermal growth factor receptor (EGFR), NCRCl Vepithelial membrane antigen (EMA) and DNA plopidy were examined. Objective quantification using image analysis (CAS 200) was applied as appropriate. Fifty cases were examined in this preliminary study. Excellent correlation between the Cytoblock preparations and parallel tissue sections was seen. Of the cancers, 81% were aneuploid with only 19% diploid in character, but 67% of the carcinomas were of histological grade 3. The mean nuclear area staining with MIBl was 31.3% and with ER was 26.7%. Twenty-four percent (24.1%) of the nuclear area showed immunoreactivity with PR. Significant immunostaining was seen in 38%, 46%, 38% and 95% of carcinomas with c-erbB-2, p53, EGFR and EMA, respectively. A significant association between histological grade of the resected tumours and both MIBl (P=0.04) and EGFR (P=0.02) expression in the Cytoblock samples was seen. p53 (P = 0.03) and EGFR (P=0.01) immunoreactivity showed an association with tumour size. EGFR (P=0.04) immunostaining also showed a relationship with the lymph node status of the patient. The technique is, we believe, a useful one for the assessment of multiple variables on breast cytology specimens; these preliminary data suggest that some of these may be useful in predicting prognosis in breast cancer patients.     

Expression of the insulin-like growth factor-I receptor in primary breast cancer and lymph node metastases: correlations with estrogen receptors alpha and beta.

Numerous laboratory studies and some epidemiological data have suggested the involvement of the insulin-like growth factor-I receptor (IGF-IR) in breast cancer development and progression. However, data on IGF-IR expression in human tissues, including breast cancer sections, are limited and often inconsistent. We therefore examined by immunohistochemistry the expression of IGF-IR in primary tumors and breast cancer metastases to lymph nodes, and correlated IGF-IR positivity with estrogen receptor (ER) status and selected clinicopathological features. We found that 1) IGF-IR was expressed in primary tumors as well as in lymph node metastases, but the expression in primary tumors was more frequent (56 % vs. 44.4 %); 2) IGF-IR expression in primary tumors was associated with negative node status (p < 0.033); 3) in node-negative primary tumors, IGF-IR positively correlated with ERbeta (p < 0.008; r = 0.538), but not with ERalpha, tumor size or grade; 4) both IGF-IR-positive and IGF-IR-negative primary tumors were found to produce IGF-IR-positive as well as IGF-IR-negative metastases; 5) in metastases, IGF-IR expression did not associate with ERalpha, ERbeta or any of the studied pathobiological markers. The results suggest that IGF-IR could become a viable pharmaceutical target in breast cancer therapy, but such therapy should be based on IGF-IR assessment in primary tumor and metastasis in each potential patient.     

Demonstration of oestrogen receptor in symptomatic breast carcinoma, using fine needle aspiration cytology

Oestrogen receptor immunocytochemical assay (ER-ICA) was used to determine oestrogen receptor (ER) content of cells in fine needle aspirate (FNA) specimens from 88 breast carcinomas. In 49 of these the radioligand binding assay for oestradiol was available for comparison. The predictive value of ER-ICA staining for a positive radioligand binding assay (greater than 10 fmol/mg protein) was 95%. Although the predictive value of negative staining was only 66%, 34 out of 37 ER-ICA negative tumours had radioligand binding assays below 60 fmol/mg protein. ER-ICA staining showed a strong positive correlation with age of the patient, positivity being rare before the menopause. There was a weak inverse correlation with tumour grade but none with tumour size or lymph node status. The assessment of ER by immunocytochemistry using FNA cytology is a rapid technique, which may easily be repeated and provides a pre-operative assessment of ER status. It allows confirmation that tumour cells are present in the sample and an assessment of tumour heterogeneity.     

雌、孕激素受体及C-erbB2在子宫内膜癌中的表达和意义

目的探讨雌、孕激素受体（Estrogen Receptor ER、Progesterone Receptor PR）及C-erbB2在子宫内膜癌中的表达与临床病理参数的关系。方法采用免疫组织化学技术检测56例子宫内膜癌患者子宫内膜中ER、PR及C-erbB2的表达,并对56例患者的临床病理资料进行回顾性分析。结果子宫内膜癌患者内膜ER、PR及C-erbB2阳性率分别为41.07%、57.14%、53.57%。子宫内膜癌中ER表达与肿瘤分化程度、年龄、有无淋巴结转移呈负相关;PR表达与肿瘤组织学类型、分化程度、年龄、浸润肌层深度及有无淋巴结转移均呈负相关;而C-erbB2的表达与内膜癌分化程度、有无淋巴结转移呈正相关。结论激素依赖型子宫内膜癌ER、PR及C-erbB2表达水平均反映了子宫内膜癌的生物学行为,三者的测定对估计预后和指导术后辅助治疗具有重要意义。     

Variation of ER status between primary and metastatic breast cancer and relationship to p53 expression*.

OBJECTIVE: Estrogen-dependent growth of breast cancer can be blocked by anti-estrogens. Estrogen receptor (ER) presence in breast cancer implies responsiveness to endocrine therapy. However, for those patients who ultimately develop resistance to endocrine therapy, the mechanisms remain unclear. The present study attempted to compare the expression status of ER mRNA in a series of primary breast tumors with matched metastases and explored the relation between ER and mutant p53 expression. METHODS: In situ hybridization using a digoxigenin-labeled estrogen receptor cDNA probe was employed to determine the expression of ER mRNA in 52 cases of primary tumors and their matched axillary lymph node metastases. Immunohistochemical staining using a monoclonal antibody against ER was also performed. RESULTS: ER expression was observed in 53.8% (28/52) of primary tumors and 48% (25/52) of metastases, while 57.7% (30/52) of primary tumors and 53.8% (28/52) of metastases showed ER mRNA positivity. There were variations in ER status between in situ hybridization and immunohistochemistry measurements and between primary tumors and metastases. Mutant p53 expression was inversely associated with ER-negative, high-grade tumors. CONCLUSIONS: In situ hybridization may be a more specific and sensitive method for determination of ER status than immunohistochemistry. It is possible that the biologic properties of ER change, and these changes may influence tumor response to endocrine therapy. In view of the ER variation, it was suggested that the ER status of metastatic tumors in addition to primary tumors should be taken into consideration in order to better determine the benefit of clinical endocrine therapy.     

Determination of Ki67 Growth Fraction and Oestrogen Receptors In Screen-Detected Breast Cancer Using Cytological Preparations

Oestrogen receptor (ER) status of 77 cases of screen-detected breast cancer has been determined using cytological preparations. In 48% ER status was positive, which was the same proportion as that formed in a control group of age-matched patients with symptomatic breast carcinoma. Since the screen-detected group contained more low grade tumours, the percentage of ER-positive cases would be expected to be higher. the reasons for the discrepancy are discussed. Ki67 score has been determined for 41 cases of screen-detected cancer. Ki67 score showed a positive correlation with histological tumour grade and a negative correlation with ER status. However, there was no correlation with tumour size or lymph node status. the Ki67 scores in the screen-detected cancers were essentially similar to those found in an age-matched symptomatic group, but the very low scores were only found in the screened group.     

Serum Thyrotropin Concentrations are not Predictive of Aggressive Breast Cancer Biology in Euthyroid Individuals

Objective: The potential influence of hypothyroidism on breast cancer remains incompletely understood. The objective of this study was to investigate the relationship between serum thyrotropin (thyroid-stimulating hormone, TSH) concentration and markers of aggressive breast cancer biology as defined by receptor expression profile, tumor grade, and American Joint Committee on Cancer (AJCC) stage characteristics.Methods: This was a retrospective cohort study of patients from 2002 to 2014. All breast cancer patients who had complete receptor (estrogen receptor, ER; progesterone receptor, PR; and human epidermal growth factor receptor 2, Her2/neu) and prediagnosis serum TSH data (n = 437) were included. All patients had 1 of 6 receptor profiles: ER+ PR+ Her2/neu-, ER+ PR- Her2/neu-, ER+ PR+ Her2/neu+, ER+ PR- Her2/neu+, ER- PR- Her2/neu+, or ER- PR- Her2/neu-. Log-transformed serum TSH concentrations were analyzed using multinomial and logistic regressions to identify potential relationships with markers of breast cancer aggressiveness.Results: Increasing serum TSH concentration was associated with a lower probability of having the receptor expression profile ER+ PR+ Her2/neu+ compared to patients with the ER+ PR+ Her2/neu- profile (odds ratio [OR] = 0.52, P = .0045). No significant associations between other receptor expression profiles and serum TSH concentration were found. All time-weighted and unweighted median serum TSH concentrations were within normal limits. No significant associations between serum TSH concentration and tumor grade, overall AJCC stage, tumor size (T), lymph node positivity (N), or presence of metastasis (M) were observed.Conclusions: Serum TSH was not associated with markers of breast cancer aggressiveness in our cohort.Abbreviations: AJCC = American Joint Committee on Cancer ER = estrogen receptor Her2/neu = human epidermal growth factor receptor 2 M = metastasis N = lymph node positivity OR = odds ratio PR = progesterone receptor T = tumor size TSH = thyroid stimulating hormone UCLA = University of California Los Angeles     

Identification of oestrogen,progesterone receptor and human epidermal growth factor receptor 2 expression in mediastinal metastases of breast cancer obtained by endobronchial ultrasound‐guided transbronchial needle aspiration

Background

In breast cancer patients, the expression statuses of oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are crucial in the choice of treatment. Receptor expression in metastatic lesions can differ from the primary tumour. The aim of our study was to analyse the utility of endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) to obtain samples allowing the identification of ER, PR and HER2 expression in patients with mediastinal metastases of breast cancer.

Patients and methods

The clinical files of all patients with a final diagnosis of breast cancer mediastinal metastases diagnosed by EBUS‐TBNA in our institution were retrospectively analysed. The ability of EBUS‐TBNA to obtain samples that allowed hormone receptor and HER2 expression analysis was calculated.

Results

Twenty‐four patients were included. ER, PR and HER2 assessments could be performed in 22, 20 and 22 patients, respectively. In 20 of the 24 patients it was possible to investigate all three types of receptor expression. In the remaining four cases, where ER, PR or HER2 expression tests could not be performed, it was due to a lack of tissue. In cases with adequate results for EBUS‐TBNA and the primary tumour agreement was greater for ER (16/19) and HER2 (12/14) than PR (8/17). Based on receptor status, there was a change in the choice of treatment for five patients.

Conclusion

In patients with breast cancer mediastinal metastases, ER, PR and HER2 expression can be assessed in samples obtained by EBUS‐TBNA whenever a sufficient tissue sample is collected.     

HR-MAS MR Spectroscopy of Breast Cancer Tissue Obtained with Core Needle Biopsy: Correlation with Prognostic Factors

The purpose of this study was to examine the correlation between high-resolution magic angle spinning (HR-MAS) magnetic resonance (MR) spectroscopy using core needle biopsy (CNB) specimens and histologic prognostic factors currently used in breast cancer patients. After institutional review board approval and informed consent were obtained for this study, CNB specimens were collected from 36 malignant lesions in 34 patients. Concentrations and metabolic ratios of various choline metabolites were estimated by HR-MAS MR spectroscopy using CNB specimens. HR-MAS spectroscopic values were compared according to histopathologic variables [tumor size, lymph node metastasis, histologic grade, status of estrogens receptor (ER), progesterone receptor (PR), HER2 (a receptor for human epidermal growth factor), and Ki-67, and triple negativity]. Multivariate analysis was performed with Orthogonal Projections to Latent Structure-Discriminant Analysis (OPLS-DA). HR-MAS MR spectroscopy quantified and discriminated choline metabolites in all CNB specimens of the 36 breast cancers. Several metabolite markers [free choline (Cho), phosphocholine (PC), creatine (Cr), taurine, myo-inositol, scyllo-inositol, total choline (tCho), glycine, Cho/Cr, tCho/Cr, PC/Cr] on HR-MAS MR spectroscopy were found to correlate with histologic prognostic factors [ER, PR, HER2, histologic grade, triple negativity, Ki-67, poor prognosis]. OPLS-DA multivariate models were generally able to discriminate the status of histologic prognostic factors (ER, PR, HER2, Ki-67) and prognosis groups. Our study suggests that HR-MAS MR spectroscopy using CNB specimens can predict tumor aggressiveness prior to surgery in breast cancer patients. In addition, it may be helpful in the detection of reliable markers for breast cancer characterization.