Positive EGFR Expression Research Articles

EGFR, HLA-G, CD70, c-MET, and NY-ESO1 as potential biomarkers in high grade epithelial ovarian carcinoma.

High grade epithelial ovarian carcinoma is an aggressive tumor. Treatment includes platinum therapy, however it recurs in most patients due to therapy resistance. In this project, we study the immunohistochemical (IHC) expression of five potential biomarkers/prognostic markers in high grade epithelial ovarian carcinoma: EGFR, HLA-G, CD70, c-MET, and NY-ESO1. A cohort of 274 patients is used. We compare the IHC expression with age, stage, ascites status, family history of cancer, disease free survival (DFS) and overall survival (OS). EGFR expression is significantly correlated with family history and worse OS. HLA-G is associated with worse OS. To confirm the results of EGFR and HLA-G, a second separated cohort of 248 patients is used. Positive EGFR expression again shows worse OS, while HLA-G expression has worse prognostic trend. CD70 has a worse OS trend. C-MET and NY-ESO1 do not have any clinical correlations. EGFR can potentially serve as target in future clinical immune therapy trials.

Expression of EGFR and p16 in Squamous Cell Carcinoma of External Auditory Canal.

The expression of EGFR and p16 in the external auditory canal squamous cell carcinoma (EACSCC) and their impacts on oncological outcomes were not well studied. Seventeen-one consecutive patients who were treated for EACSCC at Kobe University Hospital from 1995 to 2018 were enrolled in this study. The expression of EGFR, and p16 were evaluated and their impacts on oncological outcomes were statistically analyzed. Positive expression of EGFR was observed in 62 patients (87%). Strong positive expression of p16 were observed in 18 patients (32.4%), and weakly positive expression in 30 patients (42.3%), respectively. While the number of the patients with negative EGFR expression were limited, all the surgically treated patients with negative EGFR expression have been alive without disease. In the patients with T3 & T4a EACSCC, prognosis of the patients with positive p16 expression EACSCC tended to be better than those with negative p16 expression. These results suggest the clinical significance of EGFR and p16 expressions in the patients with advanced EACSCC to predict oncological outcomes.

The Co-expression of HER Family Members and CD109 is common in Pancreatic Cancer.

In the absence of biomarkers for the early detection of pancreatic cancer and the development of more effective therapeutic interventions, pancreatic cancer is projected to become the second leading cause of death from cancer in the Western world. In the past four decades, aberrant expression and activation of human epidermal growth factor receptor (EGFR, also called HER) family members have been reported in a wide range of human cancers. Currently, of the various types of drugs targeting one or more members of the HER family, only the EGFR-specific tyrosine kinase inhibitor erlotinib and more recently Zenocutuzumab, a HER-2/HER3 bispecific antibody, were granted breakthrough therapy designation by the FDA for the treatment of patients with pancreatic cancer. However, the therapeutic benefit may be modest in some patients. Hence there is an urgent need for the identification of biomarkers as prognostic indicators, therapeutic targets, and for the response to therapy and the development of more effective therapeutic agents for this highly heterogeneous cancer. In this study, for the first time, we investigated the relative expression and prognostic significance of all members of the HER family, the type-III EGFR mutant (EGFRvIII), and CD109 in tissue microarrays (TMAs) and whole tumour specimens (WTS) from pancreatic cancer patients by immunohistochemistry. We found the positive expression of wild-type EGFR (wt-EGFR) (63%, 4.7%), HER2 (75%, 14%), HER3 (none, 14%), HER4 (45%, 21%), EGFRvIII (5%, 3%), and CD109 (67%, 55%) in TMAs (USA) and WTS (UK) from pancreatic cancer patients respectively. Our results also show that the co-expression of HER family members with CD109 occurs frequently in patients with pancreatic cancer. In addition, the co-expression of HER4/CD109 may also be associated with poorer overall survival in such patients. In this article, we shall discuss these findings and their implications and future opportunities for more effective targeting of HER positive pancreatic cancer using the HER inhibitors in combination with other drugs and therapeutic interventions.

Characterization of orthotopic xenograft tumor of glioma stem cells (GSCs) on MRI, PET and immunohistochemical staining.

The orthotopic xenograft tumors of human glioma stem cells (GSCs) is a recent glioma model with genotype and phenotypic characteristics close to human gliomas. This study aimed to explore the imaging and immunohistochemical characteristics of GSCs gliomas. The rats underwent MRI and 18F-FDG PET scan in 6th-8th weeks after GSCs implantation. The MRI morphologic, DWI and PET features of the tumor lesions were assessed. In addition, the immunohistochemical features of the tumor tissues were further analyzed. Twenty-five tumor lesions were identified in 20 tumor-bearing rats. On structural MRI, the average tumor size was 30.04±17.31mm2, and the intensity was inhomogeneous in 76.00% (19/25) of the lesions. The proportion of the lesions mainly presented as solid, cystic and patchy tumor were 60.00% (15/25), 16.00% (4/25) and 24.00% (6/25), respectively. The boundary was unclear in 88.00% (22/25), and peritumoral mass effect was observed in 92.00% (23/25) of the lesions. On DWI, 80.00% (20/25) of the lesions showed increased intensity. Of the 14 lesions in the 11 rats underwent PET scan, 57.14% (8/14) showed increased FDG uptake. On immunohistochemical staining, the expression of Ki-67 was strong in all the lesions (51.67%±11.82%). Positive EGFR and VEGF expression were observed in 64.71% (11/17) and 52.94% (9/17) of the rats, whereas MGMT and HIF-1α showed negative expression in all the lesions. GSC gliomas showed significant heterogeneity and invasiveness on imaging, and exhibited strong expression of Ki-67, partial expression of EGFR and VEGF, and weak expression of MGMT and HIF-1α on immunohistochemical staining.

The role of steroid receptors, peptides and growth factors in the aetiopathogenesis of idiopathic gynecomastia.

Idiopathic gynecomastia is a diagnosis of exclusion. We aimed to evaluate the role of steroids, peptides and growth factors in these patients. Those with bilateral idiopathic gynecomastia (n=29) (Simon's grade IIb or III) who underwent gland excision were evaluated by immunohistochemical techniques using semi-quantitative grading for oestrogen receptor (ER), progesterone receptor (PR), aromatase, androgen receptor (AR), peptides (IGF-1, IGF-2, HER-2, parathyroid-hormone related peptide [PTHrP]) and growth factors (EGFR, TGFβ). The cohort comprised 29 patients, with a mean age of 25.3±5.1years and a mean body mass index of 27.2±2.3kg/m2 . Grade IIb gynecomastia was present in 79.1% and moderate-to-severe insulin resistance (HOMA-IR >3) in 53.7% of patients. ER expression was positive in 100% samples, followed by AR (96.5%), aromatase (96.5%) and PR (93.1%). IGF-1 was expressed in 86.2% of the cohort, IGF2 in 27.5% and HER-2 in only two samples, with both showing weak immunoexpression. None of the patients had positive expression of EGFR, TGF-β or PTHrP. There was no association between immunoexpression and gynecomastia grade. This study demonstrates the predominant role of oestrogen, aromatase and insulin resistance in the aetiopathogenesis of idiopathic gynecomastia and implicates the paracrine hyperestrogenic milieu in its causation as circulating hormones were normal.

Graphene quantum dots-based targeted nanoprobes detecting drug delivery, imaging, and enhanced chemotherapy of nasopharyngeal carcinoma.

One of the main clinical treatments for advanced nasopharyngeal carcinoma is chemotherapy, but systemic administration can cause serious adverse reactions. New type of nanomaterial which can actively targeting, imaging, and treating nasopharyngeal carcinoma at the same time to enhance the effect of chemotherapy, meanwhile monitoring the intracellular drug release process at the level of single cancer cell was urgently needed. GE11, an EGFR antagonist peptide, was used to target nasopharyngeal carcinoma which has positive expression of EGFR on its nucleus. GE11‐modified graphene quantum dots (GQDs@GE11) were used as drug carriers for clinical chemotherapeutics cisplatin (CDDP) and doxorubicin (DOX). The emission spectrum of GQDs (460 nm) and the excitation spectrum of DOX (470 nm) have a good overlap, thus the transfer and release process of DOX can be sensitively detected by the fluorescence resonance energy transfer (FRET). CDDP was used to enhance the chemotherapy effect of nanoprobe, and the loading amount of DOX and CDDP on GQDs@GE11 nanoprobe were up to 67 and 50 mg/g, respectively. In vivo experiments have confirmed that GQDs@GE11/CDDP/DOX nanoprobe can be enriched to tumor site through specific targeting effect, and significantly inhibit tumor cell proliferation. This new type of targeted therapy fluorescent probe provides new ideas for the study of drug release process and the treatment of nasopharyngeal carcinoma.

Immunohistochemical Expression of EGFR and ErbB2/ HER2 in Human Meningioma. A Clinicopathological Study

Background: meningioma is considered a common benign tumor and more frequent happen, they are slow growing primary tumors that originate from meningothelial cells of the arachnoid and spinal cord. The histological grade of the WHO and the extension of the initial surgical resection are determining prognostic factors in these tumors. Aim of the study: To investigate the expression of EGFR and ErbB2 / HER2 in human meningiomas, to correlate this expression with various clinic pathological parameters (age, gender, tumor type, tumor grade), and to study the correlation between these two markers. Methods: this is a retrospective study including 30 cases of human meningiomas. Clinical data collected from patient's files. Immunohistochemical study of EGFR and ErbB2/HER2 performed along with scoring. Results: this study included 30 cases of meningioma. There was a significant statistical correlation between tumor grade and tumor histological type, as 100% of grade II were atypical meningiomas, and 77.8% of grade I were meningiothelial meningiomas, with a P value 0.0001. 25/30 cases showed positive immunohistochemical expression of EGFR, 24/25 (96%) cases were grade I, 1/25 (4%), 16/25(72%) cases were meningiothelial, 1/25 (4%) case angiomatous, 1/25 (4%) case atypical, 5/25 (20%) cases were fibroblastic. only 4/30 cases showed expression of HER 2/ neu, 3/4(75%) cases were female, all cases were above 30 years of age, all cases were grade I, 2/4 (50%) cases were fibroblastic and the other two cases were meningiothelial type. Conclusions: EGFR is frequently over expressed in meningiomas, there was a significant difference between mean of EGFR and HER 2, EGFR have more positive results than HER 2.

Prognostic Impact of Membranous/Nuclear Epidermal Growth Factor Receptor Localization in Clear Cell Renal Cell Carcinoma.

EGFR is overexpressed in the majority of clear cell renal cell carcinomas (CCRCCs). Although EGFR deregulation was found to be of great significance in CCRCC biology, the EGFR overexpression is not associated with EGFR-targeted therapy responsiveness. Moreover, the prognostic role of EGFR expression remains controversial. In the present study, we evaluated the role played by EGFR overexpression in CCRCC and its prognostic significance associated with different immunohistochemical localization patterns. In our study, the Total Score (TS) related to membranous-cytoplasmic EGFR expression showed a significant correlation with grade, pathologic stage (pT), and Stage, Size, Grade, and Necrosis (SSIGN) score, and a negative correlation with nuclear EGFR expression. No significant correlations were shown between nuclear EGFR and clinic-pathological features. Additionally, a correlation between SGLT1 expression levels and pT was described. Multivariate analysis identifies pT and SSIGN score as independent prognostic factors for CCRCC. A significantly increased survival rate was found in the case of positive expression of nuclear EGFR and SGLT1. Based on our findings, SGLT1 and nuclear EGFR overexpression defines a subgroup of CCRCC patients with good prognosis. Membranous-cytoplasmic EGFR expression was shown to be a poor prognostic factor and could define a CCRCC subgroup with poor prognosis that should be responsive to anti-EGFR therapies.

Improving selection of patients with metastatic colorectal cancer to benefit from cetuximab based on KIR genotypes

AimCetuximab is a standard-of-care treatment for KRAS wild-type metastatic colorectal cancer (mCRC), but it may also be effective in a subgroup of KRAS mutant patients by its immunomodulatory activity. Here,...

Mouse Hepatocellular Carcinoma Sensitivity to Cisplatin and Docetaxel and Analysis of Related Proteins

Hepatocellular carcinoma (HCC) globally ranked fifth common cancer and the third-leading cause of death. This study aimed to characterize the new mouse hepatocellular carcinoma cell line (HCAM) for some of the most important proteins involved in cell cycle regulation P53, HER2/neu, and EGFR by immunocytochemistry. Also, to measure the sensitivity of the cells to some common chemotherapeutic agents such as cisplatin and docetaxel by the MTT cell viability assay. The findings of immunocytochemistry appeared that HCAM cells proven to express the p53 and EGFR positively when compared with the negative control. Furthermore, showing nuclear only low expression for the HER2/neu. For evaluation of the chemotherapeutic agent’s efficiency, the cells of hepatocellular carcinoma (HCAM) were treated for 72 hours using different concentrations for Cisplatin and Docetaxel. The IC50 values of docetaxel and cisplatin after 72 h exposure for HCAM was 12.82 and 10.74 respectively. Our in vitro results demonstrate that Docetaxel and Cisplatin are toxic to HCAM cell line in a concentration-dependent manner. In conclusion, our results showed positive expression of p53, EGFR, and weak HER2/neu. Also, HCAM cell line showing to be sensitive to docetaxel and cisplatin, which inhibit cell proliferation.

Oncologic Outcomes in Metastatic Colorectal Cancer with Regorafenib with FOLFIRI as a Third- or Fourth-Line Setting

BACKGROUND: To evaluate the efficacy and toxicities of regorafenib plus irinotecan, dose-escalated on the basis of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping, in previously heavily treated metastatic colorectal cancer (mCRC) and the prognostic values of EGFR expression, KRAS mutations, and tumor sidedness. METHODS: Forty-one patients with mCRC with disease progression after treatment with fluoropyrimidines, oxaliplatin, irinotecan, anti-VEGF, and anti-EGFR MoAbs were subjected to UGT1A1 genotyping and received regorafenib combined with FOLFIRI with dose-escalated irinotecan. RESULTS: The median follow-up period was 10.0 months (1.3-23.5 months). The overall disease control rate was 58.5%, whereas the median progression-free survival (PFS) and overall survival (OS) were 6.0 months and 12.0 months, respectively. KRAS mutations were significantly associated with positive EGFR expression (P = .026). KRAS mutations significantly correlated with a shorter OS than KRAS wild-type (6.0 vs. 14.4 months, P = .014) but had no significant association with PFS. Positive EGFR expression had an inverse correlation with PFS (2.5 vs. 14.0 months, P = .039) and OS (9.6 vs. 19.7 months, P = .044). Moreover, left-sided tumors associated with superior PFS (2.0 vs. 7.0 months, P < .0001) and OS (4.0 vs. 13.0 months, P < .0001), and tumor sidedness was an independent prognostic factor by the multivariate analysis. CONCLUSION: Regorafenib and FOLFIRI concomitant therapy with dose-escalated irinotecan seemed to be potentially practicable with satisfactory oncological results. KRAS mutations and EGFR expression might be predictors of poor oncological outcomes; however, left-sided mCRCs would be more beneficial for concomitant regorafenib and FOLFIRI therapy.

Concurrent radiotherapy and panitumumab after lymph node dissection and induction chemotherapy for invasive bladder cancer

PurposeIn this prospective study we evaluated safety and efficacy of concurrent radiotherapy and panitumumab following neoadjuvant/induction chemotherapy (ICT) and pelvic lymph node dissection (PLND) as a bladder preserving therapy for invasive bladder cancer (BC). Materials & MethodsPatients with cT1-4N0-2M0 bladder cancer were treated with PLND and 4 cycles of platinum-based ICT, followed by a six-and-half-week schedule of weekly panitumumab (2.5 mg/kg) and concurrent radiotherapy to the bladder (33x2 Gy)(RT/P). As primary objective, RT/P toxicity was compared to a historical control toxicity rate for concurrent cisplatin/radiotherapy (<35% of patients with Grade 3-5 toxicity). A sample size of 31 patients was estimated. Secondary end-points included complete remission (CR) at 3 months follow-up, bladder preservation rate, EGFR expression and RAS mutational status. ResultsThirty-eight patients were initially included, of whom 34 were staged cN0. After PLND, 7 (21%) patients were upstaged to pN+. Thirty-one out of 38 patients started RT/P. During RT/P, 5 patients (16%, 95% Confidence Interval, 95%CI 0-31%) experienced systemic or local grade 3-4 toxicity. Four patients did not complete treatment due to adverse events. CR was achieved in 29/31 patients (94%, 95%CI 83-100%). With a median follow-up of 34 months, 4 patients had a local recurrence for which 3 patients (10%) underwent salvage cystectomy. Two tumors had an EGFR- or RAS-mutation while 84% had positive EGFR expression. ConclusionsRT/P following ICT and PLND has a non-inferior safety profile to the historical profile of concurrent cisplatin/radiotherapy. The high CR and bladder preservation rates are promising and warrant further study.

Nimotuzumab combined with chemotherapy as first-line treatment for advanced lung squamous cell carcinoma.

BackgroundThis study was conducted to evaluate the efficacy and safety of nimotuzumab combined with chemotherapy as first‐line therapy in advanced lung squamous cell carcinoma (LSCC), and to explore predictive biomarkers of the efficacy of nimotuzumab.MethodsA retrospective study was conducted of patients with advanced LSCC administered nimotuzumab combined with chemotherapy as first‐line therapy from June 2012 to December 2016 at the Department of Respiratory Medicine, Peking Union Medical College Hospital. The associations between EGFR expression, EGFR gene copy numbers, and clinical efficacy were detected by immunohistochemistry and fluorescence in situ hybridization (FISH).ResultsTwenty‐six patients were enrolled, including 22 men and 4 women. The objective response rate was 50% and the disease control rate was 100%. The median progression‐free survival (PFS) and overall survival were 6.7 and 16.3 months, respectively. Patients whose samples were tested via FISH and showed positive EGFR expression had a trend of longer median PFS (10.0 months; P = 0.10). Adverse effects included 15 cases (57.7%) of bone marrow suppression, 15 (57.7%) of sensory neuropathy, 14 (53.8%) of alopecia, nine (34.6%) of nausea/vomiting and one case (3.8%) of elevated creatinine level. All adverse effects were attributed to chemotherapy.ConclusionNimotuzumab combined with chemotherapy might be a possible option as first‐line therapy in patients with advanced LSCC. EGFR gene copy number examined by FISH might be a possible predictive biomarker.

EGFR immunohistochemistry as biomarker for antibody-based therapy of squamous NSCLC – Experience from the first ring trial of the German Quality Assurance Initiative for Pathology (QuIP®)

BackgroundEGFR and its downstream signaling pathway are important targets for cancer therapy. Recently, the monoclonal anti-EGFR antibody Necitumumab in combination with gemcitabine and cisplatin was approved (EMA/14106/2016) for first-line treatment of squamous non-small cell carcinoma (SqNSCLC). Eligibility was restricted to cases with positive EGFR expression. In this context, a ring trial of the Quality Assurance Initiative for Pathology (QuIP®) was launched to prepare the German pathology community for a reliable and reproducible, immunohistochemically based biomarker test. Materials and methodsThe trial was set up by a three-step approach. Two lead institutes were nominated to organize the trial process and to select appropriate cancer samples. These were first tested by the H-score (range 0–300) to identify positive and negative cases. Seven additional pathology institutes with experience in EGFR immunohistochemistry each tested the selected panel of identical cases (internal ring trial) to confirm the suitability of samples and scoring criteria. Then the open ring trial for all institutes of pathology in German speaking countries was announced. ResultsFor the internal trial 8 EGFR-positive and 2 negative lung sqNSCLC samples were selected. A cut-off value of cell membranous staining in≥1% of tumor cells was introduced to define a case as EGFR negative or positive. Two points were attainable per correctly assessed sample leading to a maximum of 20 points,≥18 points were required for a successful participation. All 7 panel institute passed this barrier, 5 with the maximum of 20 points and two with one error (18 points) being related to one case with incorrect interpretation of cytoplasmic versus membranous staining and one case with an H-score of 2 as being considered EGFR positive. A second cut-off value (H-score≥3) was therefore introduced. In the open ring trial, 34 institutions participated of which 28 were successful according to the above criteria. The trial revealed a high reproducibility despite the use of different EGFR antibodies and detection systems. There was no association between technical parameters and trial failure. Again, one participant misinterpreted the subcellular EGFR localization. ConclusionsThe first nationwide ring test for determination of EGFR IHC expression in sqNSCLC could be successfully performed in a very tight time frame. By this, the national pathology community was prepared to incorporate this marker in the panel of predictive cancer tests in a quality assessed manner and to initiate and accompany future studies on EGFR pathway pathology.

Gene copy number variation and protein overexpression of EGFR and HER2 in distal extrahepatic cholangiocarcinoma

EGFR and HER2 are among the most promising therapeutic targets in solid cancers. The expression status of EGFR and HER2 are associated with the prognosis, and with a number of clinicopathological factors, in many cancers. However, few studies have examined this association in distal extrahepatic cholangiocarcinoma (EHCC). Therefore, we investigated EGFR and HER2 protein expression and gene copy number variation (CNV) in distal EHCC. We also studied the association of these factors with clinicopathological parameters and prognosis. Immunostaining, using antibodies against EGFR and HER2, was performed on 84 cases of distal EHCC. All positive (3+) and equivocal (2+) EGFR and HER2 expression cases, together with randomly selected negative (1+ and 0) cases, were evaluated for EGFR and HER2 CNV. Among distal EHCC samples, 6.0% (n=5) were positive (3+) for EGFR expression and 6.0% (n=5) were equivocal (2+). HER2 expression was positively identified in 2.4% of samples (n=2), and was equivocal in 1.2% of samples (n=1). All cases of positive EGFR expression showed amplification (n=1) or high polysomy (n=4) involving the EGFR gene; three cases (60%) of equivocal EGFR expression showed high polysomy of the EGFR gene. All cases of positive or equivocal HER2 expression (n=3, 3.6%) showed amplification of the HER2 gene. In univariate analysis, EGFR expression and CNV were associated with shorter cancer-specific overall survival (p=0.003 and p=0.018, respectively). Multivariate analysis also showed that EGFR CNV was a significant prognostic factor in distal EHCC (p=0.015). Although further study is warranted, our findings suggest that EGFR expression and CNV are factors associated with poor prognosis, and that anticancer therapeutics against EGFR and HER2 receptors may be promising therapeutic options for patients with distal EHCC.

Expression of Transforming Growth Factorα and Epidermal Growth Factor Receptor in Thyroid Carcinoma

The current study was performed on 178 paraffin embedded tissue specimens, included 111 of them were affected by thyroid carcinoma, 46 were benign neoplastic and 21individuals as control group. The study was carried out in Laboratory of College of Science, University of Wasit in collaboration with AL-Hussein Teaching Hospital and Ibn al-Bitar Laboratory Specialist in Thi Qar Province, IRAQ, from October 2015 to April 2016. Immunohistochemical technique was used to determination the expression of TGFα and its receptor EGFR in thyroid carcinoma in comparison with benign thyroid disease and control group. The aim of this study is to detect, quantify and analyze the clinicopathological correlation of those genes in patients with thyroid carcinoma. The results showed a significant increase of TGFα in thyroid patients comparing with control group and benign neoplasms, and between control group and benign neoplasms (p<0.05). On the other hand, the positive expression of EGFR was increased but did not reach to significantly difference in thyroid carcinoma in comparison with neither benign neoplasms nor control group (p>0.05). Our results concluded that there is a strong relationship between TGFα overexpression with thyroid carcinogenesis.

EGFR, COX2, p-AKT expression and PIK3CA mutation in distal extrahepatic bile duct carcinoma

Distal extrahepatic bile duct (EBD) carcinoma is a rare but highly aggressive malignant neoplasm. Some invitro studies have shown that EGFR and PI3K-Akt pathway play an important role in the carcinogenesis of bile duct carcinoma. The aim of the present study is to investigate the expression of EGFR, p-AKT, and COX-2 and the mutation of PIK3CA in distal EBD carcinoma and evaluate the association with clinicopathological factors. Ninety cases of distal extrahepatic bile duct (EBD) carcinoma specimens were studied. Immunohistochemistry (IHC) using antibodies against EGFR, p-AKT, and COX-2 was performed on TMA blocks. The PIK3CA mutation was evaluated using the PNAClamp Detection Kit from DNA samples extracted from formalin fixed, paraffin embedded tissue. EGFR expression of distal EBD carcinomas was 61.9%, 26.2%, 6.0% and 6.0% in the negative, weakly positive, moderately positive, and strongly positive groups, respectively. Positive EGFR expression showed significant relationships with high T stage (p=0.024). In Kaplan-Meier analysis, EGFR expression was associated with shorter cancer-specific overall survival (p=0.005). Multivariate analysis also showed that moderate or strong (2+ or 3+) EGFR expression was a significant prognostic factor in distal EBD carcinoma: HR 5.286; p=0.001. Ninety cases of EBD carcinoma tissue were analysed for hotspot mutations (exon 9 and 20) in the PIK3CA gene. Only one mutation was detected: a missense mutation of H1047 at exon 20. The expression levels of p-AKT and COX-2 showed no association with any clinicopathological parameters, including survival rate. Moderate and strong EGFR expressions demonstrate a direct link to poor prognosis. Although further study is warranted to understand the clinicopathological significance, our finding suggests EGFR is a useful prognostic marker of patients with distal EBD carcinoma. A low prevalence of PIK3CA mutation exists in the distal EBD carcinoma of Korean patients, indicating that mutation screening may not be useful in determining prognosis or in formulating a treatment response to targeted inhibition in Korea.

Comparative estimation of ErbB family growth receptors, Ki-67 and E-cadherin expression in pancreatic ductal adenocarcinoma cells

Aim. In immunohistochemical research of biopsy and postoperative material of 120 patients with the pancreatic ductal adenocarcinoma the levels of growth receptors of ErbB family and cancer prognostic markers expression were determined.Methods and results. Positive expression of EGFR by the tumour cells is determined in 87,5% of patients with ductal adenocarcinoma, simultaneously 77,5% of such patients had negative, and 13,33% of patients – doubtful HER-status. Expression of Ki-67 inductal carcinoma cells was found in 74,17% of patients, there were distinctions in expression of this marker within one tumour. The decline of expression of Е-cadherin was marked in 28,33% of patients with ductal adenocarcinoma, it was significantly more expressed in the areas of tumour invasion into the wall of duodenum.Conclusion. In patients with ductal adenocarcinoma direct correlation of medium strength between the levels of EGFR and HER-2/neu, EGFR and Кі-67, Кі-67 and HER-2/neu expression by the tumour cells is marked, inverse strong correlation between the level of EGFR and Е-cadherin expression, inverse correlation of medium strength between the level of expression of HER-2/neu and Е-cadherin, and between the level of Кі-67 and Е-cadherin expression there is weak inverse correlation.

Prognosis in very young women with triple-negative breast cancer: retrospective study of 216 cases.

The aim of this investigation was to compare clinical pathological characteristics and prognosis of very young and older triple-negative breast cancer (TNBC) patients in order to assess their relevance to TNBC in an younger population. Data of TNBC patients diagnosed between 2002 and 2007 were retrospectively analyzed by computer based chart information. Baseline tumor characteristics, biological markers, and patients' prognosis were compared between very young (≤ 35 years) and older (>35 years) TNBC patients. In the 216 cases of operable TNBC patients, 48 (22.2%) were ≤ 35 years and 168 (77.8%) were >35 years. Very young TNBC patients had showed a high clinical stage, more positive lymph nodes, Ck5/6 and/or EGFR expression (P = 0.049, 0.006, and 0.011, respectively). Compared to older TNBC patients, very young TNBC patients have short disease-free survival (P = 0.031), while no significant difference was found in overall survival (OS) (P = 0.075). In multivariate analysis, lymph node metastatic status was a significant predictor of OS. TNBC of very young patients is an aggressive breast cancer subtype, but the overall survival of both young and older TNBC patients did not have significant differences.

Abstract 571: Comparative immunohistochemical study of basaloid and usual squamous cell carcinoma of the esophagus

Abstract Basaloid squamous cell carcinoma (BSCC) is a rare epithelial malignancy variant of the typical SCC, and it has been associated to an aggressive behavior, with a high capacity for developing metastasis and low survival rates. It has been reported that less than 12% of the primary esophageal carcinoma have been diagnosed as BSCC. The study aimed to compare the protein expression of HER-2, EGFR, Ki-67, Cyclins A, B1 and D1 between usual SCC and BSCC. Immunohistochemistry of 94 usual ESCC and 17 EBSCC cases were carried out using Tissue Microarray technique. Immunohistochemical analysis of cyclins and growth factors receptors was based on frequency and intensity of tumor cells in each sample; Ki-67 analysis was based on the frequency of tumor cells showing strong nuclear positive staining. When the clinicopathological data were compared, only histological grade (p=0.000) showed a significant difference between the usual and basaloid SCC groups. No significant difference was found in gender, age, lymphatic, venous, and perineural invasion, pT, pN, pM and TNM staging when the two groups were compared. No significant difference was found between the overall survival rates of both groups. In EBSCC cases, cyclin A expression was positive in 94.1% of the cases, while 5.9% showed no expression. Cyclin B1 expression showed positivity in 23.6% of cases and 76.4% showed no staining. Most of the cases (70.6%) showed no cyclin D1 expression, while 29.4% were considered positive. EGFR expression was positive in 52.9% and negative in 47.1% of the cases. Expression of HER2 was observed in a small proportion of the cases (29.4%), when compared to those (70.6%) with no expression. Considering the KI-67 labeling index, most of the cases (76.4%) were classified as Low Proliferation, while only 11.8% were considered as High Proliferation. Among the ESCC cases, 30.0% were considered negative for cyclin A expression and 70.0% cases were positive. For cyclin B1, 18.4% were positive and 81.6% showed no expression. Cyclin D1 showed no staining in 85.4% of the cases, while 14.6% were positive. EGFR expression was positive in 80.9% and negative in 19.1% of the cases. HER2 expression was negative in 52.8% and 44.7% were considered positive. Analysis of Ki-67 expression showed that most of the cases (70.8%) were classified as Low Proliferation, while 29.2% were considered as High Proliferation. Comparing the markers expression between the two groups, EGFR (p=0.025) and cyclin A (p=0.029) showed significant differences. Positive EGFR expression was more frequent in the usual ESCC than in the EBSCC group. For cyclin A, positivity was more frequent in the EBSCC group, when compared to the usual ESCC cases. Regarding the other markers, there was no significant difference between the two groups. Although some observed differences did not achieve statistical significance, this work has further highlighted possible differences between the molecular pathogenesis of BSCC and SCC. Citation Format: Yukie Sato-Kuwabara, Juliano Jampietro, José Ivanildo Neves, Felipe José F Coimbra, Carolina Parucce, Wilson Luís Costa Junior, Fernando Augusto Soares. Comparative immunohistochemical study of basaloid and usual squamous cell carcinoma of the esophagus. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 571. doi:10.1158/1538-7445.AM2014-571