• Asian Pacific Journal of Cancer Prevention
• /
• 제13권3호
• /
• pp.873-877
• /
• 2012

MicroRNAs (miRNAs) are short non-coding RNA molecules characterized by their regulatory roles in cancer and gene expression. We analyzed the expression of miR-21, miR-205, and miR-342 in 59 patients with breast cancer. Samples were divided into three different groups according to their immunohistochemistry (IHC) classification: ER- positive and/or PR-positive group ($ER^+$ and/or $PR^+$; group I); HER2-positive group ($HER^{2+}$; group II); and ER/ PR/ HER2- negative ($ER^-$/ $PR^-$/ $HER^{2-}$; group III) as the triple negative group. The expression levels of the 3 miRNAs were analyzed in the tumor samples and the compared with the normal neighboring dissected tumor (NNDT) samples in all three groups. The expression of miR-21 was similar in all three groups. In patients positive for P53 by IHC, positive for axillary lymph node metastasis and higher tumor stages, it appeared to have significantly elevated. However, significant increase was not found among the 18 fibroadenoma samples. Both miR-205 and miR-342 expressions were significantly down regulated in group III. We conclude that miR-21 does not discriminate between different breast cancer groups. In contrast, miR-205 and miR-342 may be used as potential biomarkers for diagnosis of triple negative breast cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권23호
• /
• pp.10277-10280
• /
• 2015

Background and Aim: Breast cancer (BC) is a heterogeneous disease and cell proliferation markers may help to identify subtypes of clinical interest. We here analyzed the correlation between cell proliferation determined by Ki67 and HG in BC patients undergoing preoperative chemotherapy (PCT). Materials and Methods: We obtained clinical/pathological data from patients with invasive BC treated at our institution from 1999 until 2012. Expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor type 2 (HER2) and Ki67 were determined by immuno-histochemistry (IHC). Clinicopathological subtypes were defined as: Luminal A, ER and/or PR positive, HER2 negative, HG 1 or 2; Luminal B, ER and/or PR positive, HER2 negative or positive and/or HG 3; triple negative (TN), ER, PR and HER2 negative independent of HG; HER2 positive, ER, PR negative and HER2 positive, independent of HG. By using Ki67, a value of 14% separated Luminal A and B tumors, independently of the histological grade. We analyzed correlations between Ki67 and HG, to define BC subtypes and their predictive value for response to PCT. Results: 1,560 BC patients were treated in the period, 147 receiving PCT (9.5%). Some 57 had sufficient clinicopathological information to be included in the study. Median age was 52 years (26-72), with 87.7% invasive ductal carcinomas (n=50). We performed IHC for Ki67 in 40 core biopsies and 50 surgical biopsies, 37 paired samples with Ki67 before and after chemotherapy being available. There was no significant correlation between Ki67 and HG (p=0.237), both categorizing patients into different subtypes. In most cases Ki67 decreased after PCT (65.8%). Only 3 patients had pathologic complete response (cPR). Conclusions: In our experience we did not find associations between Ki67 and HG. Determination of clinicopathological luminal subtypes differs by using Ki67 or HG.

• BMB Reports
• /
• 제47권5호
• /
• pp.268-273
• /
• 2014

HER2-overexpressing breast cancers are characterized by frequent distant metastasis and often develop resistance after short-term effective treatment with the monoclonal antibody drug, trastuzumab. Here, we found that the oncogenic miRNA, miR-221, inhibited apoptosis, induced trastuzumab resistance and promoted metastasis of HER2-positive breast cancers. The tumor suppressor PTEN was identified as a miR-221 target; overexpression of PTEN abrogated the aforementioned miR-221-induced malignant phenotypes of the cells. These findings indicate that miR-221 may promote trastuzumab resistance and metastasis of HER2-positive breast cancers by targeting PTEN, suggesting its role as a potential biomarker for progression and poor prognosis, and as a novel target for trastuzumab-combined treatment of breast cancers.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권3호
• /
• pp.1655-1659
• /
• 2013

Background: HER-2/neu is a proto-oncogene that encodes a transmembrane tyrosine kinase growth factor which is crucial for stimulating growth and cellular motility. Overexpression of HER-2/neu is observed in 10-35% of human breast cancers and is associated with pathogenesis, prognosis as well as response to therapy. Given the imperative role of HER-2/neu overexpression in breast cancer, it is important to determine the magnitude of amplification which may facilitate a better prognosis as well as personalized therapy in affected patients. In this study, we determined HER-2/neu protein expression by immunohistochemistry (IHC) concurrently with HER-2/neu DNA amplification by quantitative real time-polymerase chain reaction (Q-PCR). Materials and Methods: A total of 53 paired tissue samples from breast cancer patients were frozen-sectioned to characterize the tumour and normal tissues. Only tissues with 80% tumour cells were used in this study. For confirmation, Q-PCR was used to determine the HER-2/neu DNA amplification. Results: We found 20/53 (37.7%) of the tumour tissues to be positive for HER-2/neu protein overexpression using IHC. Out of these twenty, only 9/53 (17%) cases were in agreement with the Q-PCR results. The concordance rate between IHC and Q-PCR was 79.3%. Approximately 20.7% of positive IHC cases showed no HER-2/neu gene amplification using Q-PCR. Conclusion: In conclusion, IHC can be used as an initial screening method for detection of the HER-2/neu protein overexpression. Techniques such as Q-PCR should be employed to verify the IHC results for uncertain cases as well as determination of HER-2/neu gene amplification.

• 대한간호학회지
• /
• 제12권2호
• /
• pp.67-79
• /
• 1982

The purpose of this study was undertaken to determine the nursing need of mother herself and her baby in puerperium period at home alone with percevied her role. It was hoped that this nursing information would help nurses plan effective for their nursing care. This study involved 100 postpartum mothers and the period for data collection was from May to July, 1982. The results of study were as follows; 1. The mother's mean age of 27.45, more than half of mother's was high school graduate, most of the mother have their religion, 78.4％ was housewives, and 21.6% have occupation, Their mean marriage period was 30.2 years, 61% was nuclear family with 4.2 family members and primipara was higher then multipara. 2. Most mothers showed that positive attitude for their delivery and perceived higher their mother's role. 3. Mother showed more nursing need about infant（for example, bathing, meaning of crying) than herself. 4. There was a positive correlation between mother's education, wether or not their occupation, marriage periode, parity and mother's role and their nursing need.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권2호
• /
• pp.421-425
• /
• 2015

Background: This study was performed to evaluate the amplification of HER-2/neu in patients with melanoma. Materials and Methods: Amplification of HER-2/neu was evaluated in a group of patients with melanoma, referred to two referral centers in Tehran, using immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) techniques. Results: Forty patients with mean age $57.9{\pm}19.5years$ were enrolled in this study. The most frequent type of melanoma was acral, while lower limbs were the most frequent sites. The amplification of HER2/neu was negative in 97.5% of patients with IHC and in 100% of patients with CISH technique. Only one case (2.5%) shows weak positive staining (+2) in IHC method. Fifty five percent of melanoma was ulcerative, and the most common stages of tumors were stages 4b and 3b. More than 47% of cases were in Clark level III, while the mean of Breslow thickness was $3.56{\pm}2.87mm$. The stage of the case that showed weakly positive staining (2+) in IHC was 4b. Conclusions: The amplification of HER2/neu biomarker was negative in patients with melanoma, using both CISH and IHC techniques.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권21호
• /
• pp.9233-9239
• /
• 2014

Background: We aimed to evaluate the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression discordance in matched pairs of primary breast cancer and lymph node metastasis specimens and determine the effect of discordance on prognosis. Materials and Methods: Among all patients diagnosed with lymph node metastases from 2004 to 2007, primary tumors and paired lymph node metastases were resected from 209 patients. The status of ER, PR, and HER2 expression was analyzed immunohistochemically in 200, 194, and 193 patients, respectively. Discordance was correlated with prognosis. Results: Biomarker discordance between primary tumors and paired lymph node metastases was 25.0% (50/200) for ER status, 28.9% (56/194) for PR status, and 14.0% (27/193) for HER2 status. ER positivity was a significant independent predictor of improved survival when analyzed in primary tumors and lymph node metastases. Patients with PR-positive primary tumors and paired lymph node metastases displayed significantly enhanced survival compared to patients with PR-positive primary tumors and PR-negative lymph node metastases. Patients with ER- and PR-positive primary tumors and paired lymph node metastases who received endocrine therapy after surgery displayed significantly better survival than those not receiving endocrine therapy. Similalry treated patients with PR-negative primary tumors and PR-positive paired lymph node metastases also displayed better survival than those not receiving endocrine therapy. Conclusions: Biomarker discordance was observed in matched pairs of primary tumors and lymph node metastases. Such cases displayed poor survival. Thus, it is important to reassess receptor biomarkers used for lymph node metastases.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권4호
• /
• pp.2231-2235
• /
• 2013

Background: Categorizing breast tumors based on the ER, PR and HER/Neu 2 receptor status is necessary in order to predict outcome and assist in management of breast cancer. Herfe we assessed this question in South Indian patients. Materials and Methods: A total of 619 formalin fixed paraffin embedded breast tumor tissues were collected from pathology archives after receipt of ethical clearance. With the help of primary and secondary conjugated antibodies, expression status of ER, PR and HER2/neu was determined. All the experimental data were assessed for correlations with histopathological features of tumors and clinical presentation of the subjects. Results: In the present study, the ages ranged from 20-87 years with a mean of $50.0{\pm}12.q$ years, and majority of the tumors (84%) were of infiltrating duct cell carcinoma type. Assessment of ER, PR and Her-2/neu expression showed that 46% were triple negative. Interestingly, an inverse relation between ER, PR and HER-2/neu was apparent in 41.2% (p<0.0001) of the tumors, of which 24.5% (p<0.0001) were ER and PR co-negative but HER-2 positive. Conclusions: ER and PR positive tumors are less common (i.e<30%) compared to HER-2/neu positive tumors (i.e>50%) in Indian breast cancer patients, underlining the need for effective diagnostic screening and specific therapeutic managements in order to improve the survival rate of patients in low resource countries such as India.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권22호
• /
• pp.9739-9745
• /
• 2014

Purpose: We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. Materials and Methods: The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. Results: When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. Conclusions: Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.

• Journal of Breast Cancer
• /
• 제21권4호
• /
• pp.382-390
• /
• 2018

Purpose: PIK3CA mutation is considered to be a possible cause for resistance to neoadjuvant chemotherapy (NAC) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We investigated the association between PIK3CA mutations and the outcome of NAC in HER2-positive breast cancers. Methods: A total of 100 HER2-positive breast cancer patients who had undergone NAC and surgery between 2004 and 2016 were examined. Mutation status was sequentially assessed in pre-NAC, post-NAC, and recurrent specimens taken from these patients. Results: PIK3CA mutations were identified in the sequential specimens of 17 patients (17.0%). These 17 patients experienced shorter disease-free survival (DFS) than the rest of the patients (58.3 months vs. 119.3 months, p=0.020); however, there was no significant difference in pathologic complete response (pCR) and overall survival (OS) (pCR, 17.6% vs. 33.7%, p=0.191; OS, 84.5 months vs. 118.0 months, p=0.984). While there was no difference in pCR between the wild-type and mutant PIK3CA groups in pre-NAC specimens (25.0% vs. 31.8%, p=0.199), PIK3CA mutations correlated with lower pCR in postNAC specimens (0.0% vs. 24.3%, p<0.001). Multivariate analysis revealed significantly worse DFS in the mutant PIK3CA group than in the wild-type group (hazard ratio, 3.540; 95% confidence interval, 1.001-12.589; p=0.050). Moreover, the DFS curves of the change of PIK3CA mutation status in sequential specimens were significantly different (p=0.016). Conclusion: PIK3CA mutation in HER2-positive breast cancer was correlated with a lower pCR rate and shorter DFS. These results suggest that PIK3CA mutation is a prognostic marker for NAC in HER2-positive breast cancer, especially in post-NAC specimens.