Growth Factor Receptor In Patients Research Articles

Expression Pattern of Phosphatase and Tensin Homolog and Epidermal Growth Factor Receptor in Patients with Brain Tumor

Abstract Background: The term “brain tumor” refers to a diverse group of neoplasms that originate in intracranial tissues and the meninges and range in malignancy from benign to aggressive. The epidermal growth factor receptor (EGFR) is expressed at high levels in a variety of cancers, suggesting a role in cancer etiology. Phosphatase and tensin homolog (PTEN) deleted from chromosome 10 is one of the most essential tumor suppressor genes, and it is frequently altered in brain, breast, kidney, lung, and uterine malignancies. Many people with brain malignancies have PTEN gene abnormalities. Brain tumors have proved challenging to treat, largely owing to the biological characteristics of these cancers, which often conspire to limit progress. The present study aimed to analyze the expression of EGFR and PTEN in different types of brain tumor. Methods: Tumor samples were collected. Immunohistochemistry (IHC) analysis, Western blot, and RNA expression analysis were performed to check the receptor expression. Results: IHC analysis showed the expression of EGFR in patients with meningioma, CP angle tumor, and pituitary adenoma, but no expression of PTEN was observed. In glioma, the expression of both the receptors was observed. RNA expression of PTEN was similar to control, and significantly higher expression of EGFR was observed in patients with CP angle tumor, pituitary adenoma, and meningioma. Higher expression of PTEN and EGFR was observed in glioma samples. In the present study, we have also observed the expression of EGFR, p-AKT, and p-STAT 3 in the tumor tissue samples, but no expression of PTEN was observed in CP angle, meningioma, and pituitary adenoma. Expression of both PTEN and EGFR was observed in glioma samples. Conclusion: Thus, EGFR and PTEN involved in brain tumors can be considered targets for therapeutic purposes.

Clinical Impact of Rare and Compound Mutations of Epidermal Growth Factor Receptor in Patients With Non–Small-Cell Lung Cancer

BackgroundStandard therapy of advanced non–small-cell lung cancer harboring an activating mutation in the epidermal growth factor receptor (EGFR) gene is treatment with tyrosine kinase inhibitors (TKI). However, for rare and compound mutations of the EGFR gene, the clinical evidence of TKI therapy is still unclear. Patients and MethodsA total of 2906 lung cancer samples were analyzed for EGFR mutations during routine analysis between 2010 and 2017. The samples have been investigated by Sanger sequencing and since 2014 by next-generation sequencing. ResultsWe detected EGFR mutations in 408 specimens (14%). Among these, we found 41 samples with rare and 22 with compound mutations. In these 63 samples, 56 different rare EGFR mutations occurred. Information about the clinical outcome was available for 37. Among those with rare mutations, only one patient harboring the mutation p.G874D had disease that responded to first-generation TKI therapy. In contrast, the disease of all patients with compound mutations responded to first- or second-generation TKI therapy. Furthermore, we collected data on clinical relevance regarding TKI therapy from different databases and from an additional literature search, and only found data for 36 of the 56 detected rare mutations. ConclusionInformation about the clinical outcome of patients with rare and compound EGFR mutations remains limited. At present, second- and third-generation TKIs are available, which may represent new treatment strategies for these patients. Therefore, it is becoming increasingly important to maintain databases concerning rare EGFR mutations.

Clinicopathologic and prognostic significance of human epidermal growth factor receptor in patients with gastric cancer: An updated meta-analysis.

PurposeThe aim of this update meta-analysis was to clarify the clinicopathologic and prognostic significance of human epidermal growth factor receptor(EGFR) expression in gastric cancer patients.Experimental DesignSeveral electronic databases were searched from January 1970 to May 2016. The odds ratio (OR) was calculated to assess the association between EGFR expression and pathological parameters. The hazard ratio (HR) and 95% CI were calculated to explore the relationship between EGFR expression and overall survival.ResultsFinally 7229 patients with gastric cancer from 25 eligible studies were included in the present meta analysis. High EGFR expression was found to be significantly related with tumor differentiation (OR=1.96, 95%CI: 1.14-3.34, Z=2.43, P=0.015), lymph node metastasis (OR=2.20, 95% CI: 1.63-2.96, Z=5.17, P=0.001), and tumor stage (OR=2.13, 95% CI: 1.35-3.36, Z=3.25, P=0.001). However, high EGFR expression was not significantly associated with invasion depth (OR=2.09, 95% CI: 0.4-11.05, Z=0.87, P=0.385). The pooled HR suggested that high EGFR expression was significantly correlated with overall survival (HR=1.19, 95% CI 1.04-1.37, Z=2.44, P=0.015).ConclusionsThe present meta-analysis demonstrated that high EGFR expression significantly predicts poor prognosis, suggesting that high EGFR expression may serve as a predictive biomarker for poor prognosis in patients with gastric cancer.

Expression of epidermal growth factor receptor in patients with insulin resistance and seborrheic keratomas

to study the expression of epidermal growth factor receptor (EGFR) in patients with seborrheic keratomas (SK) and insulin resistance (type 2 diabetes mellitus (DM2)) and in those without concomitant carbohydrate metabolic disturbances. 80 patients with SK were examined. According to the presence or absence of DM2, the patients were divided into 2 groups: 1) 40 patients with concomitant DM2; 2) 40 people without carbohydrate metabolic disturbances. DM2 was diagnosed on the basis of laboratory studies and an endocrinologist's consultation. Histological and immunohistochemical (IHC) examinations using anti-EGFR antibodies were performed; two intact skin sections from the patients with DM2 and two intact skin sections from those without carbohydrate metabolic disturbances were used as a control. The ICH examination using anti-EGFR monoclonal antibodies revealed that Group 1 showed intense diffuse membrane staining of more than 50% of the cells in 32 (80%) patients, moderate (30-50% cells) and weak (10-30% cells) staining in 6 (15%) and 2 (5%) patients, respectively. Marked EGFR expression was also noted in two intact skin biopsy specimens taken from patients with DM2. In Group 2, the staining intensity was weak in more than 10% but less than 30% of the SK cells in 28 (70%) patients; moderate EGFR expression was observed in 9 (22.5%) and diffuse, pronounced, staining in more than 50% of the SK cells was in 3 (7.5%) patients. The intact skin biopsy specimens taken from 2 patients without carbohydrate metabolic disturbances displayed a weak EGFR expression in the basal cell layer of the epidermis. EGFR overexpression in SK may be a result of metabolic disorders rather than a diagnostic sign of malignant neoplasms of the internal organs. The increased EGFR expression revealed in patients with SK and concomitant DM2 is caused by insulin resistance and hyperinsulinemia, in which the dysregulation of insulin signal transmission into the cell leads to changes in EGF synthesis and signaling pathway that regulates cell proliferation and growth.

Sa1729 Expression of Epidermal Growth Factor Receptor in Patients With Gastro-Oesophageal Reflux Disease and in Those With Systemic Sclerosis

Sa1729 Expression of Epidermal Growth Factor Receptor in Patients With Gastro-Oesophageal Reflux Disease and in Those With Systemic Sclerosis

Small Cell Lung Cancer with Mutation of Epidermal Growth Factor Receptor in Patients with Lung Adenocarcinoma Resistant to Gefitinib

Small Cell Lung Cancer with Mutation of Epidermal Growth Factor Receptor in Patients with Lung Adenocarcinoma Resistant to Gefitinib

Prognostic value of epidermal growth factor receptor in patients with gastric cancer: A meta-analysis

BackgroundThe epidermal growth factor receptor (EGFR) plays important roles in the development of gastric cancer. This study aims to analyze the prognostic value of EGFR in patients with gastric cancer. MethodsA meta-analysis is performed by searching Cochrane Library, PubMed, EMBASE and Science Direct databases from Jan 1970 to May 2013. Data are extracted from studies evaluating the survival of gastric cancer patients with either positive or negative EGFR expression. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) are calculated. ResultsTotally 1600 cases of gastric cancer patients from five studies are subjected to final analysis. The HR of post-operational survival of patients with positive EGFR expression is 1.16 (95% CI: 0.94–1.43) as compared with those with negative expression, indicating that positive EGFR expression does not significantly predict the poor survival of gastric cancer. ConclusionsEGFR expression is not an independent predictor for the survival of gastric cancer patients.

Clinical Significance of Serum p53 and Epidermal Growth Factor Receptor in Patients with Acute Leukemia

Pretreatment serum p53 and epidermal growth factor receptor (EGFR) were assessed using enzyme-linked immunosorbent assay (ELISA) in patients with acute leukemia to analysis their roles in characterization of different subtypes of the disease. Serum samples from thirty two patients with acute myeloid leukemia (AML) and fourteen patients with acute lymphoid leukemia (ALL) were analysed, along with 24 from healthy individuals used as a control group. The results demonstrated a significant increase of serum p53 and EGFR in patients with AML (p<0.0001) compared to the control group. Also, the results showed a significant increase of both markers in patients with ALL (p<0.05, p<0.0001 respectively). Sensitivities and specificities for these variables were 52% and 100% for p53, and 73.9%, 95.8% for EGFR. Serum p53 and EGFR could successfully differentiate between M4 and other AML subtypes, while these variables failed to discriminate among ALL subtypes. A positive significant correlation was noted between p53 and EGFR. Negative significant correlations were observed between these variables and both of hemoglobin (Hg) content and RBC count. Mutant p53 and EGFR are helpful serological markers for diagnosis of patients with AML or ALL and can aid in characterization of disease. Moreover, these markers may reflect carcinogenesis mechanisms.

Evaluation of current methods to detect the mutations of epidermal growth factor receptor in non-small cell lung cancer patients

Many different methods were developed to detect commonly known mutations and to screen new mutations of the epidermal growth factor receptor in non-small cell lung cancer patients. Some of these methods are so sensitive as to be able to detect even one epidermal growth factor receptor mutant tumor cell among up to 1000– 2000 normal cells. We have considered current methods chronologically reported to detect mutations in epidermal growth factor receptor in patients with non-small cell lung cancer. We also gave a short preview of their significance for routine clinical works. A Pub Med literature search was performed in order to demonstrate what methods are mostly used in mutation detection and to show their distribution through the last 10 years.

In vivo molecular imaging of epidermal growth factor receptor in patients with colorectal neoplasia using confocal laser endomicroscopy

Epidermal growth factor receptor (EGFR) plays an important role in tumorigenesis of colorectal cancer (CRC), and its in vivo molecular imaging in rodent models has become the subject of an increased number of studies using novel imaging techniques for gastrointestinal endoscopy. Current study aimed to evaluate the use of confocal endomicroscopy (CLE) for in vivo molecular imaging of EGFR in patients with colorectal neoplasia. Molecular imaging of colorectal neoplasia in patients was performed by CLE after topical application of a fluorescent-labeled molecular probe against EGFR. Representative images of CLE were chosen to calculate EGFR-specific fluorescence intensity. Targeted biopsy specimens were taken from each examined site during in vivo imaging for histology and immunohistochemistry (IHC). During in vivo molecular imaging in 37 patients, an EGFR-specific fluorescence signal was present in 18/19 CRC, and 12/18 colorectal adenomas. No or only weak fluorescence signal was observed in vivo in 10 cases of normal mucosa. CLE is a novel tool that could be used in molecular imaging with specific targeting of EGFR in patients with colorectal neoplasia. This technique demonstrates a promising imaging approach for targeted therapies of colorectal neoplasia.

Evaluation of current methods to detect the mutations of epidermal growth factor receptor in non-small cell lung cancer patients

Many different methods were developed to detect commonly known mutations and to screen new mutations of the epidermal growth factor receptor in non-small cell lung cancer patients. Some of these methods are so sensitive as to be able to detect even one epidermal growth factor receptor mutant tumor cell among up to 1000–2000 normal cells. We have considered current methods chronologically reported to detect mutations in epidermal growth factor receptor in patients with non-small cell lung cancer. We also gave a short preview of their significance for routine clinical works. A Pub Med literature search was performed in order to demonstrate what methods are mostly used in mutation detection and to show their distribution through the last 10 years.

The prognostic impact of epidermal growth factor receptor in patients with metastatic gastric cancer

BackgroundThe epidermal growth factor receptor (EGFR) is a potential target of anticancer therapy in gastric cancer. However, its prognostic role in metastatic gastric or gastroesophageal junction (GE) cancer has not been established yet.MethodsEGFR status was analyzed by immunohistochemistry (IHC) in paraffin-embedded samples from 357 patients who received chemotherapy in 4 first-line trials. Automated RNA extraction from paraffin and RT-quantitative PCR were additionally used to evaluate EGFR mRNA expression in 130 patients.ResultsEGFR protein expression (any grade) and overexpression (3+) were observed in 43% and 11% of patients, respectively. EGFR positivity correlated with intestinal type histology (p = 0.05), but not with other clinicopathologic characteristics. Median follow-up was 18.2 months. Median overall survival (OS) was similar in patients with EGFR positive vs. those with EGFR negative tumors, regardless whether positivity was defined as ≥1+ (10.6 vs. 10.9 months, p = 0.463) or as 3+ (8.6 vs. 10.8 months, p = 0.377). The multivariate analysis indicated that EGFR status is not an independent prognostic factor (hazard ratio 0.85, 0.56 to 1.12, p = 0.247). There were also no significant differences in overall survival when patients were categorized according to median (p = 0.116) or quartile (p = 0.767) distribution of EGFR mRNA gene expression. Similar distributions of progression-free survival according to EGFR status were observed.ConclusionsUnlike different cancer types where EGFR-positive disease is associated with an adverse prognostic value, EGFR positivity is not prognostic of patient outcome in metastatic gastric or GE cancer.

Abstract A9: Chronology of arterial hypertension and microalbuminuria associated with inhibiting treatments of vascular endothelium growth factor receptor in patients with cancer.

Abstract Purpose: Angiogenesis plays a major role in cancer. Drugs blocking the growth factor receptor in the vascular endothelium constitute a fundamental treatment in several cancers. Hypertension (HBP) and proteinuria associated with these treatments is frequent and presents in an oscillating and irregular way and is generally controlled by scarcely reliable means. Methods: We started a prospective study with the determination of microalbuminuria (MAL) in 24 hours orine samples and the execution of pre- and post-treatment 24 h-ambulatory blood pressure monitoring (ABPM) and selfmeasured of BP every 12 hours at home, during 60 days, in patients with cancer under treatment with either bevacizumab or sunitinib with a view to identifying the variations in MAL, ABPM and the onset of HBP at an early stage. For ABPM, a validated recording device was used; a recording was made prior to the start of the anti-angiogenic treatment and 20 days (at least) after the first dose. An OMRON M6 tensiometer validated by the European HBP Society was used, with the ambulatory BP figures being collected at home as per standards. MAL was measured in 24h orine samples in mg/L and mg/gr creatinine. The primary goal is to find differences of at least 16 mmHg in the mean BP between the two ABPM readings. Results: N=21. Eighteen patients received bevacizumab and three sunitinib. Mean age 57.0 years (26–79). Three patients was known to be hypertensive. Differences of 4.9 and 3.9 mmHg were found between the mean systolic and diastolic BPs before and after treatment (p&amp;lt;0.05). Conclusions: Our data revealed a statically significant increase of blood pressure in patients treated with antiangiongenics as determined by ABMP. The data point to a greater increase in nocturnal BP suggesting a non-dipper pattern. The self measured records shown an early onset HBP. Microalbuminuria trends to increase in this patients. All data will be shown at the meeting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A9.

Novel modalities in the treatment of patients with KRAS-mutated colorectal cancer

Mutations in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene are a well-described mechanism of resistance to monoclonal antibodies that target the epidermal growth factor receptor in patients with metastatic and nonoperable colorectal cancer. Treatment options in this population are limited to conventional chemotherapy regimens and antiangiogenesis compounds. Numerous strategies have been proposed in preclinical models as being effective in the presence of KRAS mutations. As basic and translational research further unravels the complex interactions and regulation points in the pathways downstream of epidermal growth factor receptor, more drugs become available for clinical testing. Indeed, there are many ongoing clinical trials that focus on the safety and efficacy of novel compounds in patients with KRAS-mutated colorectal cancer. This is a review of the literature with regard to the rationale of various approaches on this topic and also a summary of the current active clinical trials limited to patients with KRAS-mutated colorectal cancer.

Prognostic but not predictive role of platelet‐derived growth factor receptors in patients with recurrent glioblastoma

Platelet-derived growth factor receptor (PDGFR) signaling has been implicated in the pathogenesis of glioblastomas and represents a target for the tyrosine kinase inhibitor imatinib. To examine the prognostic or predictive role of PDGFRs in recurrent glioblastomas, expression was examined in tumor samples of 101 patients of CSTI571BDE40, a randomized trial comparing hydroxyurea monotherapy and a combination of hydroxyurea and imatinib. Furthermore, PDGFRα phosphorylation was investigated using in situ proximity ligation assay. PDGFRα protein was expressed in 33% of tumors and was associated with male sex, young age, presence of R132H mutated isocitrate dehydrogenase 1 protein and short median survival (142 vs. 187 days, p = 0.028). Tumor PDGFRα phosphorylation was also associated with short survival (p = 0.030). The subset of patients with PDGFRα positive glioblastoma did not have longer survival on treatment with hydroxyurea and imatinib compared with hydroxyurea monotherapy. In conclusion, both PDGFRα protein expression and phosphorylation status had a prognostic role in recurrent glioblastomas but did not define a group that showed benefit from the combination therapy consisting of hydroxyurea and imatinib.

Phosphoproteomic Analysis of Signaling Pathways in Head and Neck Squamous Cell Carcinoma Patient Samples

Molecular targeted therapy represents a promising new strategy for treating cancers because many small-molecule inhibitors targeting protein kinases have recently become available. Reverse-phase protein microarrays (RPPAs) are a useful platform for identifying dysregulated signaling pathways in tumors and can provide insight into patient-specific differences. In the present study, RPPAs were used to examine 60 protein end points (predominantly phosphoproteins) in matched tumor and nonmalignant biopsy specimens from 23 patients with head and neck squamous cell carcinoma to characterize the cancer phosphoproteome. RPPA identified 18 of 60 analytes globally elevated in tumors versus healthy tissue and 17 of 60 analytes that were decreased. The most significantly elevated analytes in tumor were checkpoint kinase (Chk) 1 serine 345 (S345), Chk 2 S33/35, eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) S65, protein kinase C (PKC) ζ/ι threonine 410/412 (T410/T412), LKB1 S334, inhibitor of kappaB alpha (IκB-α) S32, eukaryotic translation initiation factor 4E (eIF4E) S209, Smad2 S465/67, insulin receptor substrate 1 (IRS-1) S612, mitogen-activated ERK kinase 1/2 (MEK1/2) S217/221, and total PKC ι. To our knowledge, this is the first report of elevated PKC ι in head and neck squamous cell carcinoma that may have significance because PKC ι is an oncogene in several other tumor types, including lung cancer. The feasibility of using RPPA for developing theranostic tests to guide personalized therapy is discussed in the context of these data.

KRAS and BRAF Mutations and PTEN Expression Do Not Predict Efficacy of Cetuximab-Based Chemoradiotherapy in Locally Advanced Rectal Cancer

Mutations in KRAS and BRAF genes as well as the loss of expression of phosphatase and tensin homolog (PTEN) (deleted on chromosome 10) are associated with impaired activity of antibodies directed against epidermal growth factor receptor in patients with metastatic colorectal cancer. The predictive and prognostic value of the KRAS and BRAF point mutations as well as PTEN expression in patients with locally advanced rectal cancer (LARC) treated with cetuximab-based neoadjuvant chemoradiotherapy is unknown. We have conducted phase I and II trials of the combination of weekly administration of cetuximab and irinotecan and daily doses of capecitabine in conjunction with radiotherapy (45 Gy plus 5.4 Gy) in patients with LARC (stage uT3/4 or uN+). The status of KRAS and BRAF mutations was determined with direct sequencing, and PTEN expression status was determined with immunohistochemistry testing of diagnostic tumor biopsies. Tumor regression was evaluated by using standardized regression grading, and disease-free survival (DFS) was calculated according to the Kaplan-Meier method. A total of 57 patients were available for analyses. A total of 31.6% of patients carried mutations in the KRAS genes. No BRAF mutations were found, while the loss of PTEN expression was observed in 9.6% of patients. Six patients achieved complete remission, and the 3-year DFS rate was 73%. No correlation was seen between tumor regression or DFS rate and a single marker or a combination of all markers. In the present series, no BRAF mutation was detected. The presence of KRAS mutations and loss of PTEN expression were not associated with impaired response to cetuximab-based chemoradiotherapy and 3-year DFS.

Mutated KRAS results in overexpression of DUSP4, a MAP-kinase phosphatase, and SMYD3, a histone methyltransferase, in rectal carcinomas.

Mutations of the KRAS oncogene are predictive for resistance to treatment with antibodies against the epithelial growth factor receptor in patients with colorectal cancer. Overcoming this therapeutic dilemma could potentially be achieved by the introduction of drugs that inhibit signaling pathways that are activated by KRAS mutations. To identify comprehensively such signaling pathways, we profiled pretreatment biopsies and normal mucosa from 65 patients with locally advanced rectal cancer-30 of which carried mutated KRAS-using global gene expression microarrays. By comparing all tumor tissues exclusively to matched normal mucosa, we could improve assay sensitivity, and identified a total of 22,297 features that were differentially expressed (adjusted P-value <0.05) between normal mucosa and cancer, including several novel potential rectal cancer genes. We then used this comprehensive description of the rectal cancer transcriptome as the baseline for identifying KRAS-dependent alterations. The presence of activating KRAS mutations is significantly correlated to an upregulation of 13 genes (adjusted P-value <0.05), among them DUSP4, a MAP-kinase phosphatase, and SMYD3, a histone methyltransferase. Inhibition of the expression of both genes has previously been shown using the MEK1-inhibitor PD98059 and the antibacterial compound Novobiocin, respectively. These findings suggest a potential approach to overcome resistance to treatment with antibodies against the epithelial growth factor receptor in patients with KRAS-mutant rectal carcinomas.

Can patient-reported kidney cancer–specific symptoms at baseline serve as an indicator for median progression-free and overall survival in sorafenib-refractory metastatic renal cell carcinoma?

6136 Background: Baseline health-related quality of life and symptom burden have been shown to be predictive of survival in patients with cancer. The Functional Assessment of Cancer Therapy–Kidney Cancer Symptom Index (FKSI) is used to measure symptom burden in patients with renal cell carcinoma (RCC). The main objective of this study was to determine the relationship between baseline FKSI scores and median progression- free survival (mPFS) and median overall survival (mOS) after treatment with axitinib, a potent inhibitor of vascular endothelial growth factor receptors in patients with sorafenib-refractory metastatic RCC (mRCC). Methods: As part of a multicenter, open-label, phase II study of patients with sorafenib-refractory mRCC treated with axitinib, patients reported symptoms at baseline using the FKSI, with higher scores indicating less severe symptoms (FKSI-15 range, 0 to 60; FKSI-Disease Related Symptoms [DRS] range, 0 to 36). A Weibull (fully parametric) model was fit to time-to-event data to establish the relationship of baseline FKSI score with mPFS and mOS. Kaplan-Meier curves were obtained as sensitivity analyses. Results: Sixty-two patients with sorafenib-refractory mRCC were evaluated. Longer progression-free and overall survival times were associated with higher (more favorable) baseline FKSI-15 and FKSI-DRS scores. For example, for FKS-15 scores of 0 (most symptoms), 30, and 60 (no symptoms), respectively, the mPFS were 0.72, 3.83, and 20.43 months, and the mOS were 1.05, 6.27, and 37.53 months. Similar patterns and interpretations were observed for the FKSI-DRS scores. These results from the parametric model were supported by the results from the Kaplan-Meier analyses. Conclusions: In patients with sorafenib-refractory mRCC treated with axitinib, baseline patient-reported kidney cancer symptoms were linked to mPFS and mOS in a clear and interpretable way. These results support the evaluation of patient-reported symptoms at baseline in clinical trials and in clinical practice to measure symptom severity and potentially predict progression-free and overall survival outcomes. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Bayer, Genentech, Novartis, Pfizer, Wyeth Abbott Laboratories, Pfizer Bayer, Genentech, Novartis, Pfizer, Wyeth

Expression of p16 protein and epidermal growth factor receptor in patients with adenocarcinoma of the uterine cervix: an immunohistochemical analysis

The present study assessed the expression of p16 and epidermal growth factor receptor (EGFR) in patients with adenocarcinoma of the uterine cervix to determine their influence on prognosis and to evaluate a possible association between their expression and various clinicopathologic parameters. p16 and EGFR expression was investigated by immunohistochemistry from paraffin-embedded tissue in 39 patients with adenocarcinoma of the uterine cervix. The immunohistochemical findings were correlated with different clinicopathologic parameters of the patients. p16 was expressed in 56% of the patients. A trend towards increased lymph vascular space invasion was observed in p16 positive tumors (p = 0.06). There was no statistically significant association between p16 expression and clinical stage, age, histology, tumor size, tumor grade, lymph node status and recurrence disease (p > 0.05). p16 expression did influence neither disease-free nor overall survival (p > 0.05). EGFR was expressed in 44% of the patients. There was no statistically significant correlation between EGFR expression and clinical stage, age, histology, tumor size, tumor grade, lymph vascular space invasion, lymph node status and recurrence disease (p > 0.05). EGFR expression did influence neither disease-free nor overall survival (p > 0.05). p16 and EGFR are frequently expressed in adenocarcinoma of the uterine cervix. Our study observed a trend towards increased lymph vascular space invasion in p16 positive tumors. Otherwise, the expression of the investigated parameters did not correlate with any clinicopathologic parameters and had no influence on overall and disease-free survival. So far, the investigation of p16 and EGFR is of limited use to assess patients' prognosis and guide clinical management.