HER2 Research Articles

Evaluation of prognostic significance of microRNA in tumors of luminal, primary operable breast cancer without Her2 neu overexpression in postmenopausal women.

e12558 Background: Breast cancer (BC) is associated with miRNAs, the qualitative and quantitative analysis of which shows significant differences between molecular subtypes, as well as between miRNAs circulating in the bloodstream and detected in tumor tissue. Since there is no clear characteristics for markers of luminal B primary operable BC without Her 2 neu overexpression, our purpose was an evaluation of prognostic significance of miRNA-21, 221, 20a, 200a, 196a in such postmenopausal patients in order to create a diagnostic panel. Methods: The study included 120 samples of healthy tissues of patients with luminal A BC (group 1, mean age 76.16±3.14 years) and tumor tissues of patients with luminal B BC (group 2, mean age 69.5±3.2 years); invasive ductal carcinoma in all patients. The expression status was analyzed using 5 mioRNA markers associated, according to the literature, with various molecular subtypes of BC (miRNA-21, 221, 20a, 200a, 196a). The Thermo Scientific PureLink RNA Mini Kit was used for the total RNA isolation. The reverse transcription reaction was performed using the ImProm-II Reverse Transcriptase kit (Promega). The Livak/2 method was used to assess the relative expression of miRNAs. Results: The average relative expression was: miRNA-21 in group 1 – 0.2±0.01, group 2 – 1.5±0.05; miRNA- 221 in group 1 – 0.19±0.02, group 2 – 0.43±0.04; miRNA -20a in group 1 – 0.12±0.01, group 2 – 0.13±0.01, miRNA -200a in group 1 – 0.22±0.02, group 2 – 0.96±0.06; miRNA- 196a in group 1 – 1.06±0.02, group 2 – 1.56±0.04. The differences between the groups were statistically significant (p = 0.0001); the difference was statistically insignificant only for miRNA -20a (p = 0.159955). Conclusions: Results of the study allow considering the overexpression of miR-21, 221, 200a and 196a and the relatively low expression of miR-20a as diagnostic markers for a diagnostic panel for luminal B BC without overexpression of HER2/neu.

Metaplastic breast cancer: A retrospective analysis over 14 years.

e13066 Background: Metaplastic breast carcinoma (MBC), a rare entity, is known to be an aggressive form of breast cancer. With few published reports and scant literature, there are no current guidelines for this type of cancer. The aim of the study is to describe the patient characteristics, pathologic features, treatment and clinical outcomes of the patients with MBC at our institution. Methods: A retrospective analysis of patient charts with histologically confirmed MBC from 2001 to 2014 was done. Clinical information was abstracted from the medical records. Medical records were reviewed for patient age, tumor size, nodal status, tumor grade, hormone receptor status, treatment, recurrence rates and survival characteristics. Results: Twenty-three patients were identified with a median age at diagnosis of 59 years (range 42-91 years). The median tumor size was 2.1 cm (range 0.4-4.5 cm). Most tumors were grade 3 (73.9 %). None of the patients had metastatic disease at presentation. 17 patients were node negative (74%). 13 patients (56.5 %) were triple negative. 6 patients (26 %) underwent mastectomy and 17 underwent lumpectomy. 16 out of 23 patients underwent post-operative radiation therapy. The 5-year disease free survival was 73.9 % and 5-year overall survival was 82.6%. The tumor size was more than or equal to 2.4 cm in all the patients with recurrence. 60 % of the patients with recurrence were triple negative and 20% were Her2 neu positive. 33.33 % patients were poorly differentiated on histology. Conclusions: Based on our analysis and review of literature, MBC has higher tumor grade, hormone receptor negativity and lesser nodal involvement on presentation. Various studies have shown that tumor size is often large on presentation. In our study, tumor size was modest on presentation. Hence, our survival rates are better than seen with other studies. As per our analysis and as demonstrated by other studies, tumor size is an independent risk factor for recurrence. Other ominous factors for recurrence are triple negative hormone status and poorly differentiated tumor as seen in our case. Further studies and clinical trials comparing with infiltrating ductal carcinoma are needed to understand this rare breast cancer.

Breast cancer: The Indian scenario.

e12567 Background: This study was undertaken to evaluate the clinic-pathological characteristics and outcome of patients with female breast cancer at I.R.C.H, AIIMS, New Delhi, one of the largest tertiary-care cancer center in India. Methods: This ambispective study included patients with breast cancer in females, registered at our institute from January 1st, 2014 to December 31st, 2018.We retrieved data from prospectively maintained clinical case records. Results: We included 997 patients with median age of 47.5 years (21–90) The TNM (AJCC-7th edition) stage distribution was stage I, 40 (4.01%); stage II, 326 (32.70%); stage III, 419 (42.02%); and stage IV, 212 (21.26%). The median tumour diameter was 5 cm. Infiltrating ductal carcinoma (96%) was the most common histologic subtype. Fifty eight percent of cases were positive for ER or/ and PR whereas 30.89% patients were HER2/neu positive. Triple negativity was found in 29.88 % of cases. Patients underwent breast conserving surgery in 28.2% of cases, 41.7% were received neo-adjuvant chemotherapy and 9.5 % of patients offered palliative chemotherapy. The pathological complete response was seen in 20.5% of cases. Loco-regional recurrence occurred in 2.8%, and 23.2% of patients developed distant metastases. The discordance of receptor was present in 20.5% for ER, 25.1% for PR, and 15 % for HER2/neu on re-biopsy at the time of relapse . Only 37.83% of the eligible patients received trastuzumab upfront. For non- metastatic group, the median time of relapse was 36 months, 3 year relapse free survival (RFS) was 73.5% and overall survival (OS) was 82.1% . Clinical stage(stage III), triple negativity and HER2 neu positivity were associated inferior RFS however pathological node involvement (HR 1.4, 95% CI 1.01–2.18, p = 0.01) and triple negativity (HR 1.9, 95% CI 1.36–2.90, p = 0.001) were associated with poor OS . For metastatic group, the median time of progression was 18 months and 3 year progression free survival (PFS) was 35% and OS was 20%. More than 2 sites of metastasis, upfront brain metastasis, triple negativity, and poor performance status (ECOG III/IV) were associated with inferior survival. Conclusions: This is one of the largest comprehensive data from a single center. Majority of our patients are younger in age, advance in stage, aggressive in biology and unaffordability of targeted therapy on eligible patients might lead to poor overall outcome. Triple negativity is found in around 30% of cases and associated with poor survival.

Survival outcomes of metaplastic breast carcinoma: An Indian tertiary care center data.

e12579 Background: Metaplastic breast carcinoma is a rare histological subtype that has basal like characteristics and is reported to have a poorer prognosis than no specific type/ductal carcinoma (ductal/NST). We aimed to investigate clinicopathological features and outcome from a single institution based registry. Methods: Clinical records of breast cancer patients treated during 2012-2019 were screened and 31 cases of metaplastic breast carcinoma were found. Descriptive analysis was done for patients’ demographics and clinicopathological features. Kaplan Meier method was used to assess survival outcomes. Results: The incidence of metaplastic breast cancer was 0.5% (31/6180) in our study out of which the most common histopathological differentiation was squamous (45.16%). The second most common was sarcomatoid histology (32.25%), followed by chondroid (9.68%) and mixed histology (12.9%). The median age at diagnosis was 60 years ranging from 28 to 82 years. 64.15% of patients were post-menopausal. At presentation, three (9.67%) patients had metastatic disease while the rest were diagnosed with early (51.61%) and locally advanced cancers (38.72%). Triple negative cancers (ER/PR/Her2 negative) constituted the vast majority with 22 cases (80.6%) while hormone receptor positive (ER/PR positive, Her-2 negative) and Her-2 neu positive (ER/PR negative) made up the rest with three patients (9.67%) each group respectively. The median overall survival was found to be 39 months (95% CI 25.46 - 52.53). Conclusions: After a thorough search in PubMed and Google Scholar, we could not find a larger case series from India with clinical outcomes for metaplastic breast carcinoma. Our results suggest that metaplastic breast carcinoma is a heterogenous disease. Outcomes of metaplastic breast carcinoma are relatively worse when compared with literature for triple negative breast cancer and breast cancer in general. Further biological understanding may offer valuable insights for newer targets and therapeutic approaches to metaplastic breast cancer.

Her-2 neu expression in cervical intraepithelial neoplasia and carcinoma of cervix

Currently radiotherapy, cisplatin based chemo-radiation and surgery are used in combination for treating cervical cancer according to stage of the tumor. Patients with advanced disease stage have limited treatment options with median overall survival of less than one year. Therefore, there is increasing interest in using targeted therapy as a treatment modality. There are controversial views of various authors regarding role of Her-2 neu targeted therapy in cervical carcinoma. The present study was conducted to evaluate the expression of Her-2 neu in Pre-malignant and Malignant lesions of cervix and attempt its correlation with histological type, grade and stage of the tumor. A cross-sectional observational study was conducted from January 2017 to January 2018 including a total of 55 patients with either pre-malignant and malignant lesions of cervix. Rabbit monoclonal Antibody to Her2/ErBb2 from BioGenex was used for staining. Intensity of Her-2 neu expression was graded according to the 2014 ASCO/CAP guidelines for Her-2 reporting. There was higher expression of Her-2 neu expression in HSIL then LSIL. There was significant correlation between Her-2 neu expression and histological types of malignant lesions. There was no significant correlation between Her-2 neu expression and pre-malignant lesions, stage of cervical carcinoma and grades of squamous cell carcinoma. Her-2 neu has a role in higher grade of cervical lesions but studies with larger cohorts are needed to comment upon its definite role in targeted therapy.

STUDY ON TWO YEAR SURVIVAL OF STAGE II AND STAGE III BREAST CARCINOMA IN EASTERN INDIA WITH SPECIAL REFERANCE TO PROGNOSTIC MARKERS HER-2/NEU, ER, PR AND Ki-67.

Breast cancer is one of the most commonly diagnosed malignancies and leading cause of cancer death in women over the world and the second most common cancer in females in India. Length of survival of cancer patients is an important indicator for knowing the outcome of treatment in any study. As the disease burden and mortality rate is very high, knowing the factors that influence survival rates among women with breast cancer may help design early detection and improve treatment. The immunohistochemistry plays a very important role in prognostication and treatment determination.
 Aim: This study aims to correlate the various relevant prognostic pattern like reactivity pattern of ER,PR,Her-2/Neu ,ki-67 and 2-yr overall survival.
 Material and method: The proposed study was a cross sectional study with mostly prospective observation and with some retrospective observation, included 74 patients of stage II and stage III breast carcinoma who underwent MRM in Chittaranjan National Cancer Institute from 2017-2018. The various clinical and histopathological prognostic parameters with Estrogen/ Progesterone hormone receptors and Human epidermal growth factor receptor (Her-2/Neu) status in invasive breast carcinoma patients were studied and correlated.
 Result: 58.1%, 54.1% and 35.1% of the cases were ER, PR and Her-2/neu positive respectively.
 89.2% of cases had Ki-67 level >20%. Her-2 neu negative, ER negative and KI-67>20% were found to be significant factors for mortality. Maximum (66.7%) of patients with recurrence and maximum (53.8%) patients who died in study period had triple negative breast cancer. Triple negative tumours have poor survival as compared to ER + PR + and HER-2/Neu +ve tumours. Disease free survival and overall survival of the patients with Ki-67< 20% was better than that of patients with Ki-67>20% (100%).
 Keywords: Breast cancer, Invasive ductal carcinoma, ER,PR,HER-2/Neu , Ki-67 , Two year survival.

The Histological Subtypes of Breast Cancer Seen in a Tertiary Hospital in South-East, Nigeria

INTRODUCTION: Breast cancer is a disease with heterogeneous nature that may have different prognosis and respond to therapy differently despite similarities in histological type, grade and stage. It is common among women in both developed and developing countries of the world. 
 
 MATERIALS AND METHODS: This study was a 2-year retrospective study involving a systematic analysis of all the formalin-fixed paraffin-embedded tissue blocks previously diagnosed as breast cancers. The study occurred at the Department of Morbid Anatomy, University of Nigeria Teaching Hospital, Enugu. We retrieved all the archived tissue blocks and subjected them to further ancillary testing using the immunohistochemistry monoclonal antibodies: (Oestrogen receptors (ER), Progesterone receptors (PR) and Her-2 neu antibodies).
 
 RESULTS: Out of 417 cases of breast cancer analysed, four hundred and Ten (410) were females representing 98.3%, seven (7) were males representing 1.7%. The mean age of all subjects in this study was 45.1±10.2 SD (years). The age of patients ranged from20 to 70 years. The age group 31 to 40 years showed the highest number of cases, 133 (32.4%). The cases positive for ER were 157 (37.6%), while 260 (62.4%) were negative. The cases positive for PR were 144 (34.5%) and 273 (65.5%) were negative. Fifty-four cases (12.9%) were HER2-neu positive, 15 (3.6%) were equivocal and could not be further analysed due to lack of the facility to do Fluorescence in-situ hybridisation, and 348 (83.5%) were HER-neu negative. Phenotypic classification based on ER, PR, and Her2 immunohistochemistry showed 113 cases (27.1%) were Luminal A, 45 cases (10.8%) were Luminal B, 23 cases (5.5%) were Her2 Enriched, 236 cases (56.6%) were Basal-like/Triple-negative, and none (0%) was Normal-like.
 
 CONCLUSION: In conclusion, this study shows that Basal-like/Triple-negative breast cancers are most common and are seen more in premenopausal women in Enugu.

Efficacy and safety of oral pyrotinib in HER2 positive metastatic breast cancer: real-world practice

Pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising antitumor activity and acceptable tolerability in phase II and phase III randomized clinical trials. We assessed the activity and safety of oral pyrotinib for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer patients in the real world. We retrospectively analyzed 72 HER2 positive metastatic breast cancer (MBC) patients who received oral pyrotinib based regimens at Beijing Cancer Hospital and other four hospitals (Peking University First Hospital, China-Japan Friendship Hospital, General Hospital of PLA, Peking University Third Hospital) from August 2018 to September 2019. Progression free survival (PFS), objective response rate (ORR), adverse events (AE) of pyrotinib were investigated. Seventy-two patients with HER2 positive MBC were enrolled. The median age of the patients was 55 years (range: 32-79 years). Sixty-nine (95.8%) patients had received anti-HER2 treatment in the metastatic and/or (neo) adjuvant settings; 61 (84.7%) patients had received anti-HER2 treatments in the metastatic setting in terms of trastuzumab 56 (77.8%) patients, lapatinib 36 (50.0%) patients, and T-DM1 4 (5.6%) patients. Among these 72 patients who received oral pyrotinib based regimens, 62 (86.1%) patients received pyrotinib (±trastuzumab) in combination with chemotherapy, 6 (8.3%) patients received pyrotinib (± trastuzumab) in combination with endocrine therapy and 4 (5.6%) patients received pyrotinib (±trastuzumab). Sixty-five (90.3%) patients received 400 mg pyrotinib once daily as initial dose, and 7 (9.7%) patients received 320 mg. OBJECTIVE response and safety to pyrotinib based therapy were evaluable in all the 72 patients. One (1.4%) patient achieved complete response (CR), 18 (25.0%) patients achieved partial response (PR), 41 (56.9%) patients had stable disease (SD), and 12 (16.7%) patients had progressive disease (PD). The ORR (CR+PR) was 26.4% and the median PFS was 7.6 months (95%CI: 5.5-9.7 months). Among the 36 patients with prior lapatinib therapy, the median PFS was 7.9 months (95%CI: 4.1-11.7 months). Among the 15 patients with brain metastasis, the median PFS was 6.0 months (95%CI: 2.2-9.8 months). The main toxicities related to pyrotinib were diarrhea in 57 (79.2%) cases, and 48 (66.7%) cases with grade 1-2 as well as 9 (12.5%) cases with grade 3. Pyrotinib based therapy is an effective treatment for patients with HER2 positive MBC, including patients with lapatinib treatment failure and brain metastasis, and the toxicities can be tolerated.

Whole-lesion histogram analysis of apparent diffusion coefficient for the prediction of pathological complete response to neoadjuvant chemotherapy in different subtypes of breast cancer

Objective To investigate the value of whole-lesion histogram parameters of apparent diffusion coefficient (ADC) in evaluating and predicting the pathological complete response(PCR) to neoadjuvant chemotherapy (NAC) in different subtypes of breast cancer. Methods This retrospective study included 117 patients with breast cancer who underwent MRI examination before NAC prior to surgery from January 2016 to December 2017 in the First Affiliated Hospital of Nanjing University. All cases were divided into Luminal B, HER2 positive (n=21) and triple negative (n=26) groups. The surgical pathology after chemotherapy was evaluated by Miller-Payne (M-P) system and the patients were divided into PCR group and non-PCR (nPCR) group. Firevoxel software was used to generate the whole-lesion ADC histogram. The parameters included mean (ADCmean), skewness, kurtosis, the minimum (ADCmin), the maximum (ADCmax), 10th percentile(ADC10%), 50th percentile (ADC50%) and 90th percentile (ADC90%). The two independent samples t test or Mann-Whitney U test was used to compare the differences between PCR and nPCR groups in each subtype. The diagnostic performance of statistically different ADC parameters for predicting PCR was evaluated by receiver operating characteristic (ROC) curve. Results Kurtosis was significantly higher in PCR group than that in nPCR group in HER2 positive subtype (P=0.039). It achieved an area under the curve (AUC) of 0.813 with sensitivity of 100% and specificity of 68.7% at the optimal cutoff value (1.861) for differentiating PCR from nPCR cases. In triple negative subtype, ADCmean and ADC50% were smaller in PCR group than those in nPCR group (P=0.028,0.013). They achieved AUCs of 0.800, 0.842, respectively. When ADCmean of 1.030×10-3 mm2/s and ADC50% of 0.976×10-3 mm2/s were used as cutoff value to differentiate PCR from nPCR, the sensitivities were 75.0%, 80.0% and the specificities were 83.3%, 83.3%, respectively. Conclusion Kurtosis can predict post-NAC PCR in patients with HER2 positive breast cancer, while ADC50% has a high value in predicting post NAC PCR of triple negative breast cancer patients. Key words: Breast neoplasms; Molecular subtype; Neoadjuvant chemotherapy; Magnetic resonance imaging

Bevacizumab plus paclitaxel not cost effective for HER2− MBC

Bevacizumab plus paclitaxel not cost effective for HER2− MBC

HER2 Expression in Gastric Cancer and Gastroesophageal Junction Cancer

Background: Carcinoma of the stomach is a major cause of cancer mortality worldwide. Due to social impact of gastric carcinoma (GC), there is a need to stratify patients into appropriate screening, surveillance and treatment programs. Although histopathology remains the most reliable and less expensive method, numerous efforts have been made to identify and validate novel biomarkers to accomplish the goals. In recent years, several molecules have been identified and tested for their clinical relevace in GC management. Among the biomarkers with the exception of HER2, none of the biomarkers is currently used in clinical practice, and some of them were described in single studies.
 Materials and Methods: This prospective type of observational study was performed in the Department of Surgery, Dhaka Medical College Hospital, Dhaka, 6 months from approval of protocol. Total 45 consecutive patients aged 18 years and above without consideration of gender were selected purposefully. Every patient was evaluated by clinical examination, appropriate investigations and after a confirm diagnosis of the tissue from the cancer. All patients have undergone operative intervention and Gastrectomy specimens were subtotal (including cardiac and pylorus), subtotal (including the pylorus), total radical gastrectomy and oesophago-gastrectomy sample. All specimens obtained were immersed in 10% formalin. Samples of whom were sent to the department of pathology, DMCH for histopathology examination. Portion of representative tissue/block was sent to AFIP (Armed Forces Institute of Pathology, Dhaka) for immunohistochemistry to find out the HER2 expression in gastric cancer and gastro-oesophageal cancer. Data was collected in a pre-designed questionnaire by face to face interview.
 Result and observation: In this study when 45 cases were categorized according to WHO grading system it was observed that majority (30) patients were found in grade II, among them 3(10%) were HER2 positive. But with grade III tumour the HER2 positivity were found more i,e; 37.5% (3/8). Grade- I tumor show HER2 neu expression 28.57% (2/7) and according to location most of the cases with HER2 positive expression was located in the gastro-esophageal junction which is 27.27% (3/11) than gastric carcinoma which is 14.70% (5/34).
 Conclusion: Most of the patients of gastric and gastrooesophageal junction adenocarcinoma are diagnosed at a very late stage, so they require special attention in treatment protocol, including chemotherapy and immunotherapy for increasing their survivability. The study showed with poorly differentiated (high grade) tumour, the HER2 positivity were found more.
 Journal of Surgical Sciences (2018) Vol. 22 (2) : 79-82

Clinical comparison between ductal carcinoma in situ and ductal carcinoma in situ with microinvasion

Objective To analyze the differences in the treatment patterns, clinical characteristics, treatment outcomes and prognostic factors between breast cancer patients with ductal carcinoma in situ (DCIS) and ductal carcinoma in situ with microinvasion (DCIS-MI). Methods Clinical data of 866 female patients including 631 DCIS cases and 235 DCIS-MI cases treated in our institution between 1999 and 2013 were retrospectively analyzed. The local control (LC), disease-free survival (DFS) and overall survival (OS) rates were calculated by Kaplan-Meier survival analysis. The prognostic factors were identified by Log-rank test. Results Similar LC, DFS and OS rates were obtained between two groups (all P>0.05). The univariate analysis demonstrated that Her-2-positive patients had worse OS and DFS than Her-2-negative counterparts. Patients undergoing breast-conserving surgery without radiotherapy had lower LC and DFS rates compared with those receiving radical mastectomy. Conclusions DCIS and DCIS-MI patients have similar clinical prognosis in terms of OS, LC and DFS. Her-2 positive is an unfavorable prognostic factor for DFS and OS. The LC and DFS rates in the breast-conserving surgery alone group are worse than those in the mastectomy group. Key words: Breast ductal carcinoma in situ; Breast ductal carcinoma in situ with microinvasion; Breast neoplasm/radiotherapy; Breast neoplasm/surgery; Prognosis

Analysis of the factors influencing the pathological complete remission and prognosis of young breast cancer patients after neoadjuvant chemotherapy

Objective To explore the clinicopathological factors that influence the prognosis and pathological complete response (PCR) of young breast cancer patients after neoadjuvant chemotherapy. Methods From January 2007 to December 2017, 87 cases of female breast cancer patients aged ≤40 who received neoadjuvant chemotherapy and were admitted to the breast surgery department of Qingdao 8th people′s hospital were analyzed retrospectively.According to the pathological results, , the patients were divided into three groups: 30 in the PCR group and 57 in the non PCR group. To compare the correlation between the composition of PCR, recurrence/metastasis and death and clinicopathological characteristics, and to analyze the relationship between PCR and disease-free survival(DFS) and overall survival(OS). Results After neoadjuvant chemotherapy, 30 of the 87 patients reached to PCR (34.5%). The proportion of PCR after neoadjuvant chemotherapy in young breast cancer is related to estrogen receptor (ER), progesterone receptor (PR), preoperative lymph node status, Ki67 level and molecular typing( χ2 values were 3.592, 4.614, 8.373, 4.251 and 14.569, respectively, P values were 0.047, 0.032, 0.039, 0.039 and 0.006, respectively; the proportion of recurrence and metastasis patients with Er, PR and human epidermal growth factor receptor 2 2, HER-2, tumor size and lymph node status were correlated (χ2 values were 8.778, 6.243, 9.413, 14.910, 23.074, P values were 0.003, 0.013, 0.009, 0.002, < 0.001, respectively); the proportion of dead patients was correlated with Er, PR, HER-2, grade, tumor size and lymph node status (χ2 values were 6.686, 4.340, 11.874, 15.707, 12.428, 26.564, respectively, P values were 0.010, 0.037, 0.003, < 0.001, 0.006, < 0.001). Er, PR, HER-2, tumor size, preoperative lymph node status and molecular typing were correlated with DFS (HR(95%CI) was 0.53 (0.31-0.93), 2.12 (1.21-3.64), 0.46 (0.27-0.77), 1.91 (1.40-2.62), 2.22 (1.55-3.20), 1.21 (0.95-1.55), all P< 0.05), while er, PR, HER-2, classification, tumor size and preoperative lymph node status were closely correlated with OS (HR(95%CI was 0.47 (0.23-0.98), 2.14 (1.03-4.44), 0.37 (0.19-0.76), 2.90 (1.45-5.79), 1.86 (1.24-2.79) and 2.22 (1.39-3.56), respectively (all P < 0.05)). Among the 33 patients with recurrence and metastasis, 5 (16.7%)patients had PCR, while the remaining 28 (49.1%)patients had not reached PCR, accounting for 49.1% (28/57) of all the non PCR patients. The difference between the two groups was statistically significant (P = 0.019). Among the 21 patients who died, there were 2 patients with PCR, accounting for 6.7% (2/30) of all the patients with PCR; the remaining 19 patients did not reach PCR, accounting for 33.3% (19/57) of all the patients without PCR. The difference between the two groups was statistically significant(P= 0.026). Conclusion The proportion of PCR, DFS and OS in young breast cancer patients after neoadjuvant chemotherapy were affected by many clinicopathological factors. Key words: Young breast cancer; Neoadjuvant chemotherapy; Pathological complete remission rate; Disease-free survival; Overall survival

Clinico-pathological co-relation using various immuno-histochemistry markers likeER, PR, HER-2 NEU, CK5/6, EGFR, KI-67 in carcinoma breast

In India, for the year 2012, 144,937 women were newly detected with breast cancer and 70,218 women died of it. For every 2 women newly diagnosed with breast cancer, one lady is dying of it. The aim of this study is to evaluate clinical parameters and pathological findings including various Immuno-histochemistry (IHC) markers like ER, PR, HER-2 NEU, CK5/6, EGFR, Ki-67 in cases of carcinoma breast and classify them into molecular classification based on IHC markers and try to correlate them clinically. This prospective, observational study was carried out in 56 patients with early carcinoma breast (stage-I and stage-II) and IHC evaluation for various markers was done. Data was analysed by using Molecular Classification, divide them into estrogen positive (luminal HER-2, luminal A and luminal B) and estrogen negative (Triple negative or basal cell type, HER-2Neu type and normal breast like phenotype) subtypes. We had correlated this data with parameters like age of the patient, clinical and pathological staging of the breast carcinoma, presence or absence of nodes and presence or absence of other IHC parameters. We used ANOVA-F test to catagories variables and measure the test of significance. On IHC in Her-2 neu equivocal cases (patients who had two “++” positive points), we performed FISH test. Out of these 17 equivocal cases, only 3 were positive, 10 were negative and 4 patients did not underwent this test due to several reasons. Finally, Ki-67 value is significantly high in triple negative and Luminal-B patients. NPI is also having low ‘P’value, although not reaching the level of significance. Types of breast carcinoma, which look histologically similar behaves differently in their clinical presentation and in prognosis.In our study only Ki-67 was correlated with poor prognostic subtype of molecular classification but no any poor risk of clinical or histological parameter was correlated significantly with bad prognostic subtype of molecular classification as Luminal-B or triple negative type. We can say that this molecular classification is different in terms of prognosis in patients with similar looking clinical and histological parameters.

Regulation of signaling pathways associated with cardiac valve development

Congenital heart disease is the most common birth defect in China, of which heart valve dysplasia is an important phenotype.Heart valve development is an important process of embryonic development, which is regulated by a variety of signaling pathways.If the process of proliferation, differentiation or migration of endothelial cells and cardiomyocytes is abnormal, the heart valve will develop abnormally and the valvular heart disease may occur.Tissue explant systems and various animal model experiments have demonstrated that multiple signaling pathways interact to form a vast regulatory network that collectively regulates the development of heart valves.This review will highlight the nost intensively studied signaling pathways in epithelial-mesenchymal transition, including VEGF, NFATc1, Notch, Wnt, TGF-β, ErbB, and NF1 signaling pathways. Key words: Cardiac valve; VEGF; NFATc1; Notch; Wnt; TGF-β; BMP; ErbB; NF1

Expression and clinical significance of lysophosphatidic acid receptor 5 protein in breast cancer

Objective To investigate the expression and clinical significance of lysophosphatidic acid receptor 5 (LPA5) protein in breast cancer tissues. Methods The specimens of breast cancer tissues and adjacent tissues of 80 breast cancer patients from January 2015 to December 2016 in the First People's Hospital of Yongkang were selected in the study.The expression of LPA5 in breast cancer tissues and adjacent tissues was determined by immunohistochemistry.The clinical case characteristics of patients were collected. Results The positive expression rate of LPA5 in breast cancer tissues(72.5%) was higher than that in adjacent tissues(8.75%)(χ2=67.394, P 0.05). There were no significant differences in the positive expression rates of LPA5 in the breast cancer tissues among luminal type, human epidermal growth factor receptor 2 (Her2) overexpressing type and triple negative type (P>0.05). The disease-free survival rate(86.3%) and overall survival rate(87.5%) of patients with negative expression of LPA5 in breast cancer tissues were higher than those in breast cancer tissues with positive expression (65.0%, 66.3%)(χ2=4.517, 4.328, all P<0.05). Conclusion LPA5 expression is up-regulated in breast cancer tissues, and LPA5 may be involved in the development and progression of breast cancer, which is closely related to the prognosis of breast cancer. Key words: Breast neoplasms; Immunohistochemistry; Receptors, lysophosphatidic acid; Prognosis; Staging; Lymph node metastasis; Survival

Expression and prognosis of N-α-acetyltransferase gene 10 in breast cancer

Objective To study the possibility of protein acetyltransferase gene 10 (NAA10) as a target for breast cancer treatment. Methods Based on METABRIC database, 1974 cases of breast cancer patients were selected, including 718 cases of Luminal A subtype, 488 cases of Luminal B subtype, 240 cases of human epidermalgrowth factor receptor-2 (Her-2) subtype, 329 cases of basal-like subtype, and 199 cases of normal-like subtype. Using METABRIC database, the relationship between 33 acetyltransferase genes and the prognosis of breast cancer, and the relationship between NAA10 gene expression and clinicopathological parameters of breast cancer were studied. NAA10 small interfering RNA (siRNA) was used to treat breast cancer cell lines with NAA10 high expression, and the effect of NAA10 gene silencing on breast cancer cell proliferation was detected by cell counting kit-8 (CCK-8) and plate clone formation assays. Results The mRNA expression of NAA10 was significantly correlated with the disease-free survival rate (DFS) and overall survival rate of breast cancer (P<0.05), and the relative risk ratios were 1.31 (1.14-1.51) and 1.13 (1.01-1.25), respectively. NAA10 gene expression was positively correlated with breast cancer histological grade, lymph node status, and Nottingham index (NPI) (P<0.01). NAA10 mRNA and protein levels were highest in Basal-like breast cancer. Compared with control group, NAA10 gene silencing inhibited 50% breast cancer cell proliferation (P<0.05). Conclusion NAA10 gene is closely related to breast cancer cell proliferation and its expression level is closely related to breast cancer prognosis. NAA10 gene may become a target for future treatment of breast cancer. Key words: N-α-acetyltransferase gene 10; Lysine acetyltransferase; Small interfering RNA; Breast cancer

Comparison of Cerb B2 expression and Ki-67 index with modified scarff-bloom-richardson grading system in invasive ductal carcinoma

Aim: Breast cancer is the most frequent cancer among women. Cerb B2 is an oncogene that encodes a transmembrane glycoprotein known as HER-2 protein or receptor. Ki-67 is nuclear protein associated with cellular proliferation. In this study, we investigated the relationships between the histopathologic parameters in the “Modified Scarff-Bloom-Richardson” microscopic grading and expression of Cerb B2 and Ki-67 index gene in cases with invasive ductal carcinoma. Breast cancer is the most common type of cancer in women, but also the second most common cause of death after lung cancer.Material and Methods: In this study examined 45 patients who were diagnosed with invasive ductal carcinoma between January 2017 and January 2019 in Sivas Cumhuriyet University, department of surgical oncology. Cases, Cerb B2 expression and Ki-67 index were retrospectively screened from pathology recordsResults: Increased expression of Cerb B2 was statistically significant related with increased tubule formation, pleomorfism, mitosis rate, and histological grade (p=0.006, p=0.027, p0.001, p=0.001, respectively). Increased Ki-67 index was statistically significant related with increased tubule formation, pleomorphism, mitosis rate, and histological grade (p=0.031, p0.001, p=0.048, p=0.010, respectively).Conclusion: As a result, it was observed that there was a positive correlation between parameters included in Modified Scarff-Bloom-Richardson grading system with Cerb B2 expression and Ki-67 index. Cerb B2 and Ki-67 index are important prognostic biomarkers in human breast cancer.

Clinicopathological significance of immunohistochemical expression of Filamin A in breast cancer.

BACKGROUND:Filamin A is an actin-crosslinking protein expressed in many malignancies, although its prognostic and therapeutic role in breast cancer is not studied. There is enigma regarding its dual role in cancer, the tumor-progressing or tumor-suppressing effects depending on the site to which it localizes in the cell. The current study aimed to detect Filamin A expression in breast cancer and its association with other biomarkers and other clinicopathological parameters and established risk factors in breast cancer so that it can be a potential site for targeted therapy.MATERIALS AND METHODS:One hundred female patients of histologically proven breast cancer who presented to our hospital over a 2-year period were included in the study. None of the patients received prior radiotherapy, chemotherapy, or immunotherapy. Patients with recurrent breast cancer are not included in the study. All study cases are subjected to immunohistochemistry for estrogen receptor, progesterone receptor, Her2 neu, and ki-67 from core biopsy tissue of cases diagnosed as breast carcinoma. Tissue sections were subjected to immunohistochemistry with anti-Filamin A.RESULTS:Filamin A is expressed in 69% of cases of invasive breast cancer in our study. There was no statistically significant relationship of Filamin A immunoexpression with histological grade, age, parity, oral contraceptive use, smokeless tobacco use, TNM staging, clinical staging, clinical prognostic staging, and also ER, PR, Her2 neu, and ki-67 status (P > 0.05). Thus, it appears to be an independent biomarker in breast carcinoma. Filamin A was expressed only in the cytoplasm in all our study cases. Filamin A expression can be observed in adjacent normal breast tissue and benign fibroadenoma tissues also, but the pattern of expression is mainly membranous with cytoplasmic positivity. The cytoplasmic expression is seen in malignant cells as well as normal breast and benign tumor sections implicating the dual role of Filamin A in breast cancer.CONCLUSION:No significant correlation could be found between Filamin A expression and clinicopathological parameters in our study. The cytoplasmic expression is seen in malignant cells as well as normal breast and benign tumor sections implicating the dual role of Filamin A in breast cancer. Filamin A immunoexpression should be further correlated with metastasis-free survival period of breast cancer patients

Identification of Candidate Biomarkers for Idiopathic Thrombocytopenic Purpura by Bioinformatics Analysis of Microarray Data.

Idiopathic Thrombocytopenic Purpura (ITP) is a multifactorial disease with decreased count of platelet that can lead to bruising and bleeding manifestations. This study was intended to identify critical genes associated with chronic ITP. The gene expression profile GSE46922 was downloaded from the Gene Expression Omnibus database to recognize Differentially Expressed Genes (DEGs) by R software. Gene ontology and pathway analyses were performed by DAVID. The biological network was constructed using the Cytoscape. Molecular Complex Detection (MCODE) was applied for detecting module analysis. Transcription factors were identified by the PANTHER classification system database and the gene regulatory network was constructed by Cytoscape. One hundred thirty-two DEGs were screened from comparison newly diagnosed ITP than chronic ITP. Biological process analysis revealed that the DEGs were enriched in terms of positive regulation of autophagy and prohibiting apoptosis in the chronic phase. KEGG pathway analysis showed that the DEGs were enriched in the ErbB signaling pathway, mRNA surveillance pathway, Estrogen signaling pathway, and Notch signaling pathway. Additionally, the biological network was established, and five modules were extracted from the network. ARRB1, VIM, SF1, BUB3, GRK5, and RHOG were detected as hub genes that also belonged to the modules. SF1 also was identified as a hub-TF gene. To sum up, microarray data analysis could perform a panel of genes that provides new clues for diagnosing chronic ITP.