鼻咽癌组织中EGFR和nm23基因表达与预后关系研究

目的 探讨表皮生长因子受体(EGFR)和转移抑制基因(nm23)表达与鼻咽癌(NPC)患者预后的相关性.方法 回顾分析本院2003-2006年放疗前行鼻咽活检且资料完整的127例经病理证实的鼻咽癌患者,所有患者均采用6 MV X线调强放疗联合顺铂+氟尿嘧啶方案化疗.采用免疫组化链霉素抗生物素蛋白-过氧化物酶法(SP)检...     

Expression of Y-Box-binding protein 1 in Chinese patients with breast cancer

The purpose of this study was to investigate the expression of Y-Box-binding protein 1 (YB-1) in breast cancer and its correlation with clinicopathological characteristics and prognosis. Paraffin sections were retrospectively collected from 239 cases of stage I–III breast cancer patients and 30 healthy females who received surgery between January 2000 and December 2004 in the Chinese People’s Liberation Army General Hospital. The protein expression of YB-1 was detected by immunohistochemistry. The expression difference between the two groups and the correlation between YB-1 expression and clinicopathological characteristics and breast cancer prognosis were analyzed. Within the breast cancer group, YB-1 was expressed in the cytoplasm in 100.0% (239/239) of cases and in the nucleus in 36.8% (88/239) of cases. Within the control group of normal breast tissue, YB-1 was expressed in the cytoplasm in 100.0% (30/30) of cases and in the nucleus in 16.7% (5/30) of cases. The expression of YB-1 in the nucleus of breast cancer cells was significantly higher than that in normal breast tissue (P = 0.029). The expression of YB-1 in the nucleus of breast cancer cells positively correlated with the Scarff–Bloom–Richardson grade (P = 0.007) and HER-2 expression (P = 0.005), negatively correlated with ER expression (P = 0.004), and was independent of the age, menstrual status, pathological type, tumor size, lymph node status, presence of thrombosis, PR expression, and EGFR expression. The 5-year disease-free survival (DFS) and overall survival (OS) of patients with positive YB-1 expression in the nucleus were significantly lower than those of patients who were negative for nuclear YB-1 expression, and the difference was statistically significant (DFS 65.9% vs. 82.1%, P = 0.000; OS 79.5% vs. 92.1%, P = 0.000). Multivariate analysis suggested that the expression of YB-1 in the nucleus is an independent prognostic factor that affects DFS and OS in breast cancer patients (DFS P = 0.015; OS P = 0.035). In conclusion, the expression of YB-1 in the nucleus is related to carcinogenesis and the development of breast cancer. Therefore, YB-1 is an important molecular marker that can be used to predict breast cancer prognosis.     

Prognostic effect of activated EGFR expression in human colon carcinomas: comparison with EGFR status

Background:

Evidence suggests that epidermal growth factor receptor (EGFR)-activation status may better predict the clinical behaviour of colon cancers than does EGFR expression. However, the prognostic effect of phospho-EGFR in primary colon cancer remains undefined.

Methods:

Phospho-EGFR (Tyr-1173) and EGFR expression were analysed by immunohistochemistry (IHC) in tissue microarrays of TNM stage II and III colon cancers from completed adjuvant therapy trials (n=388). Staining intensity was scored and correlated with clinicopathological variables, DNA mismatch repair (MMR) status, rates of cell proliferation (Ki-67), apoptosis (caspase-3), and patient survival.

Results:

Phospho-EGFR expression was detected in 157 of 388 (40%) tumours, whereas EGFR was found in 214 of 361 (59%). Although phospho-EGFR was unrelated to clinicopathological variables, strong EGFR intensity was associated with higher tumour stage (P=0.03). Tumours overexpressing EGFR (P=0.0002) or phospho-EGFR (P=0.015) showed increased Ki-67, but not caspase-3 expression. Phospho-EGFR was not prognostic. EGFR intensity was associated with worse disease-free survival (DFS) (hazard ratio (HR): 1.21 (1.03, 1.41); P=0.019) and overall survival (OS) (HR: 1.19 (1.02, 1.39); P=0.028). Tumours expressing both EGFR and phospho-EGFR had similar survival as EGFR alone. Stage and lymph node number were prognostic for DFS and OS, and histological grade for OS. EGFR was an independent predictor of DFS (P=0.042) after adjustment for stage, histological grade, age, and MMR status.

Conclusion:

Phospho-EGFR and EGFR expression were associated with tumour cell hyperproliferation. Phospho-EGFR was not prognostic, whereas increased EGFR intensity was independently associated with poor DFS.     

Preoperative serum carbohydrate antigen 125 level is an independent negative prognostic marker for overall survival in colorectal cancer

To evaluate the prognostic value of preoperative serum carbohydrate antigen19-9 (CA19-9), carcinoembryonic antigen (CEA), and carbohydrate antigen 125 (CA125) for overall survival (OS) in patients with colorectal cancer (CRC). Preoperative serum CA19-9, CEA, and CA125 levels were detected by C12 protein chip diagnostic system in 80 patients with CRC, and the association of their preoperative status with the patients’ OS was analyzed. Patients with positive preoperative serum CA19-9, CA125, and CEA had a worse survival comparing with those negative patients, the difference in CA19-9 and CA125 reached statistical significance (Log rank test, P < 0.05), but the difference of CEA did not achieve statistical significance (Log rank test, P > 0.05). The OS of patients with CRC with three positive tumor markers (TMs) <1 or 2 positive TMs < negative TM, simultaneously positive serum CA19-9, CEA, and CA125 was the most dismal predicting factor for OS. Spearman correlations revealed that the preoperative serum status of CA19-9 (P = 0.000), CEA (P = 0.000), and CA125 (P = 0.000) had correlations with stage; the preoperative serum CA125 status (r = −0.385, P = 0.000) and stage (r = −0.457, P = 0.000) and location (r = 0.223, P = 0.047) had correlations with OS. Multivariate analysis with Cox regression model showed that only stage (P = 0.000) and the preoperative serum CA125 status (P = 0.016) were independent prognostic factors for OS of patients with CRC. The preoperative status of serum CA19-9, CEA, and CA125 had correlations with CRC stage. The simultaneously positive serum CA19-9, CEA, and CA125 was the most dismal predicting factor for OS of patients with CRC. Preoperative serum CA125 status and stage were independent prognostic factors for OS of CRC.     

头颈部癌表皮生长因子受体表达及对预后判断价值

[目的]探讨表皮生长因子受体(EGFR)在头颈部癌组织中表达情况及其对预后判断的价值。[方法]从2002年12月至2003年12月对91例经病理证实的初治头颈部癌(HNC),其中鼻咽癌(NPC)87例,头颈部鳞癌(HNSCC)4例的活检标本,应用免疫组织化学技术检测EGFR在癌组织中的表达情况。对有完善病历资料的61例HNC(其中NPC58例),探讨EGFR表达与临床病理特点及生存关系。[结果]在91例HNC中EGFR阳性74例,总表达率81.3%。87例NPC中阳性71例,表达率81.6%;4例HNSCC中阳性3例,表达率75%。61例HNC中,EGFR表达与性别、年龄、总分期、T分期、N分期无相关性。EGFR阳性组与阴性组3年总生存率(OS)、无病生存率(DFS)、无区域复发生存率(LRFS)、无远处转移生存率(DMFS)分别为73.5%、63.3%、71.4%、65.3%和90.0%、90.0%、90.0%、90.0%,但单因素分析其差异无显著性。在其中58例NPC中,EGFR表达与性别、年龄、总分期、T分期、N分期无相关性。EGFR阳性组和阴性组3年OS、DFS、LRFS、DMFS分别为72.3%、63.6%、72.2%、63.8%和100.0%、100.0%、100.0%、100.0%。在单因素分析中,两组3年DFS和DMFS有显著性差异(P<0.05),但在多因素分析未发现有显著性差异。[结论]EGFR在HNC中表达率较高,过度表达者呈现不良预后的趋势,但未获得统计学差异。     

Promyelocytic leukemia (PML) gene expression is a prognostic factor in ampullary cancer patients

Background: Promyelocytic leukemia (PML) tumor suppressor gene plays a key role in acute PML pathogenesis but its involvement in pathogenesis and prognosis of solid cancers has not been defined yet.Patients and methods: In all, 62 ampullary adenocarcinoma patients who underwent curative surgery between 1996 and 2005 were included. Expression analysis of PML was carried out by immunohistochemical staining and correlated with disease-free survival (DFS) and overall survival (OS).Results: In 24 tumor specimens (38.7%), PML was classified as absent, in 16 (25.8%) as focally expressed and in 22 (35.5%) as diffusely expressed. By univariate analysis, DFS was significantly influenced by pathological T stage (P = 0.03), lymph nodal involvement (P = 0.002), and PML expression (P = 0.001). DFS in patients without PML expression was 28.0 months versus 45.1 and 75.5 for patients with focal and diffuse expression, respectively. OS in the group of patients without PML expression, with focal expression, and with diffuse expression was 40, 48, and 77 months, respectively (P = 0.002). By a multivariate analysis, PML expression was the strongest prognostic factor for DFS (P = 0.003) and the only statically significant prognostic factor for OS (P = 0.009).Conclusions: Our preliminary data suggest PML as a novel prognostic tool for ampullary cancer patients.     

Comparison of laparoscopic and open radical gastrectomy for gastric cancer patients with GLIM-defined malnutrition

PurposeMalnutrition is common in the patients with gastric cancer. Radical gastrectomy remained the primary strategy of curable treatment for gastric cancer. This study is performed to explore the effect of laparoscopic radical gastrectomy on clinical outcomes in gastric cancer patients with malnutrition.MethodsGastric cancer patients with GLIM-defined malnutrition between 2014 and 2019 at our center were enrolled. The patients were divided into two groups according to the different type of surgery. Propensity score match analysis was used to balance the clinicopathologic characteristics of two groups. Postoperative outcomes and survival were compared. Multivariate analysis was used to independent risk factors of complication, overall survival (OS), and disease-free survival (DFS).ResultsCompared with patients underwent open radical gastrectomy, patients who underwent laparoscopic radical gastrectomy had lower rate of total, surgical and severe complications. They also had shorter postoperative hospital stay with better OS and DFS. Hypoalbuminemia (P = 0.003) was the independent risk factor of complications. Old age (≥75, P = 0.035) and TNM stage (III: P < 0.001, II: P = 0.015) were the independent risk factors of OS. Combined resection (P = 0.003) and TNM stage (III: P < 0.001, II: P = 0.001) posed independent risk factors of lacking DFS. Laparoscopic surgery proved to be the independent protective factor of complications (P = 0.014), OS (P < 0.001) and DFS (P < 0.001).ConclusionLaparoscopic radical gastrectomy was relative safe and showed favorable outcomes in malnourished gastric cancer patients.     

Meta-analysis of concomitant compared to sequential adjuvant trastuzumab in breast cancer: the sooner the better

Adjuvant trastuzumab (T) significantly reduces the risk of progression and death in HER-2 positive high-risk early breast cancer. The differential benefit of T, administered either sequential or concomitant, has been calculated with 2 comparative meta-analyses of randomized trials. We have meta-analyzed sequential and concomitant arms of 6 T adjuvant trials separately and then calculated the pooled hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS) in both meta-analyses. Primary cardiac event rates have also been meta-analyzed. In the concomitant T meta-analysis, HRs for DFS and OS were 0.62 and 0.68, respectively (P < 0.0001 and <0.00001 for both endpoints). Conversely, in the sequential T meta-analysis, HRs for DFS and OS were, respectively, 0.74 and 0.87, where P is, however, significant only in the first comparison (P < 0.00001 and P = 0.09). Relative risks (RRs) for major cardiac events (severe cardiac hearth failure or death) are 2.44 (P = 0.07) in the concomitant T meta-analysis and 8.35 (P < 0.0001) in the sequential T meta-analysis. Concomitant adjuvant T therapy seems to give a significant and greater benefit than sequential administration in both DFS and OS, and the number of cases of severe cardiotoxicity does not seem to be higher in concomitant administration than in the sequential one.     

Impact of alcohol consumption on survival in patients with esophageal carcinoma: A large cohort with long‐term follow‐up

Alcohol is a well‐established cause of esophageal carcinoma, but its effect on survival is little known and contradictory. To clarify whether drinking is an independent predictor of survival in esophageal carcinoma, 2151 Chinese patients, receiving surgical resection from January 1997 to December 2008, were followed until March 2014. Cox proportional hazards analysis was applied to evaluate the prognostic effect of alcohol consumption. The median follow‐up was 64 months. The median overall survival (OS; 42 months) and disease‐free survival (DFS; 33 months) for never‐drinkers were significantly higher than ever‐drinkers (27 and 22 months, respectively). In the multivariate Cox model that was adjusted for age, weight loss, stage according to criteria set by the American Joint Committee on Cancer, radicality of surgery, adjuvant treatment, smoking status, and gender, the hazard ratios of ever‐drinking were 1.22 (1.06–1.41, P = 0.005) on OS, and 1.16 (1.01–1.34, P = 0.037) on DFS. The hazardous effect on OS and DFS of drinking grew statistically significantly in a dose‐dependent manner with increasing amount of alcohol consumption per day (both P‐value for trend < 0.05). The predictive effect of drinking on OS (P = 0.596) or DFS (P = 0.207) was not significant in the subgroup with esophageal adenocarcinoma (n = 195). The current study revealed that the survival is shortened, of those patients who consume alcohol before diagnosis of esophageal squamous cell carcinoma, which are not attributable to differences in stage, smoking status, and gender. Alcohol control should be emphasized to reduce mortality of esophageal carcinoma, and further outcome studies should include alcohol as a potential prognosticator.     

Preliminary results of a phase III randomized study comparing chemotherapy neoadjuvantly or concurrently with radiotherapy for locoregionally advanced nasopharyngeal carcinoma

The current study was conducted to compare neoadjuvant chemotherapy (NACT) with concurrent chemotherapy for efficacy, toxicities and compliance of locoregionally advanced nasopharyngeal carcinoma (NPC). Eligible patients were randomized to NACT + radiotherapy (RT) + adjuvant chemotherapy (AC) arm or concurrent chemoradiotherapy(CCRT) + AC arm. Two arms received same conventional RT at a planned dose of 70 Gy. Neoadjuvant chemotherapy comprised cisplatin 90 mg/m² (30 mg/m²/day) and 5-fluorouracil 1,500 mg/m² (500 mg/m²/day) over 3 days for two 21-day cycles. The same regimen at equal dosage was administered on the 1st and 22nd days of the radiotherapy as concurrent chemotherapy. Four cycles of the same chemotherapy regimen were given to both two arms as AC. A total of 338 NPC patients were recruited. 170 patients were randomized to NACT arm and 168 patients to CCRT arm. The median duration of follow-up was 38 months. The 3-year OS and DFS rates were 95.9 versus 94.5% (P = 0.54) and 78.5 versus 82.5% (P = 0.16), respectively, in NACT and CCRT arms. An unplanned subgroup analysis according to the N-classification suggested that CCRT improves MFS in patients with N0-1 disease (80.1 vs. 94.9%, P = 0.034). Among the acute toxicities observed, the rates of grade 3/4 mucositis (52.4 vs. 35.9% P = 0.023) and vomiting (13.7 vs. 4.7% P = 0.000) were significantly higher in CCRT arm. Our preliminary results only showed an advantage of CCRT over NACT in NPC patients with limited N disease in MFS. More acute toxicities were observed in CCRT arm and a trend of better tolerance was observed in NACT arm.     

Epidermal growth factor receptor and AKT1 gene copy numbers by multi‐gene fluorescence in situ hybridization impact on prognosis in breast cancer

The epidermal growth factor receptor (EGFR)/PI3K/AKT signaling pathway aberrations play significant roles in breast cancer occurrence and development. However, the status of EGFR and AKT1 gene copy numbers remains unclear. In this study, we showed that the rates of EGFR and AKT1 gene copy number alterations were associated with the prognosis of breast cancer. Among 205 patients, high EGFR and AKT1 gene copy numbers were observed in 34.6% and 27.8% of cases by multi‐gene fluorescence in situ hybridization, respectively. Co‐heightened EGFR/AKT1 gene copy numbers were identified in 11.7% cases. No changes were found in 49.3% of patients. Although changes in EGFR and AKT1 gene copy numbers had no correlation with patients' age, tumor stage, histological grade and the expression status of other molecular makers, high EGFR (P = 0.0002) but not AKT1 (P = 0.1177) gene copy numbers correlated with poor 5‐year overall survival. The patients with co‐heightened EGFR/AKT1 gene copy numbers displayed a poorer prognosis than those with tumors with only high EGFR gene copy numbers (P = 0.0383). Both Univariate (U) and COX multivariate (C) analyses revealed that high EGFR and AKT1 gene copy numbers (P = 0.000 [U], P = 0.0001 [C]), similar to histological grade (P = 0.001 [U], P = 0.012 [C]) and lymph node metastasis (P = 0.046 [U], P = 0.158 [C]), were independent prognostic indicators of 5‐year overall survival. These results indicate that high EGFR and AKT1 gene copy numbers were relatively frequent in breast cancer. Co‐heightened EGFR/AKT1 gene copy numbers had a worse outcome than those with only high EGFR gene copy numbers, suggesting that evaluation of these two genes together may be useful for selecting patients for anti‐EGFR‐targeted therapy or anti‐EGFR/AKT1‐targeted therapy and for predicting outcomes.     

GPR30 and estrogen receptor expression: new insights into hormone dependence of inflammatory breast cancer

GPR30 is a novel G protein-coupled estrogen receptor (ER) associated with metastases in breast cancer (BC) and poor survival in endometrial and ovarian tumors. The association of GPR30 expression with inflammatory breast cancer (IBC), an aggressive and commonly hormone-independent form of BC, has not been studied. GPR30, ER, progesterone receptor (PR), epidermal growth factor receptor (EGFR), and HER-2 expression were assessed by immunohistochemistry (and FISH for HER-2) in 88 primary IBCs. GPR30 expression was correlated with patient overall survival (OS), disease-free survival (DFS), pathologic variables, and other biomarkers. GPR30 expression was found in 69% of IBC cases. ER, PR, HER-2, and EGFR were found in 43, 35, 39, and 34% of IBC cases, respectively. GPR30 expression correlated inversely with ER expression (P = 0.02). Co-expression of ER and GPR30 was found in 24% of IBC samples; 19% expressed only ER and 46% expressed only GPR30. Univariate analysis showed no association between GPR30 expression and OS or DFS. However, co-expression of ER and GPR30 was associated with improved OS (P < 0.03) and marginally with DFS (P < 0.06); the absence of both ER and GPR30 was associated with worse OS and DFS (P = 0.03 for both). Multivariate analysis identified ER as an independent prognostic factor of OS (P = 0.008) and DFS (P = 0.02). The majority of IBC tumors are GPR30-positive, suggesting that estrogen signaling may be active in ER-negative IBC patients. These findings suggest potential new therapeutic targets for IBC such as novel endocrine agents or direct modulation of GPR30.     

Prognostic value of nutritional risk screening 2002 scale in nasopharyngeal carcinoma: A large‐scale cohort study

Little is known about the value of the nutritional risk screening 2002 (NRS2002) scale in nasopharyngeal carcinoma (NPC). We conducted a large‐scale study to address this issue. We employed a big‐data intelligence database platform at our center and identified 3232 eligible patients treated between 2009 and 2013. Of the 3232 (12.9% of 24 986) eligible patients, 469 (14.5%), 13 (0.4%), 953 (29.5%), 1762 (54.5%) and 35 (1.1%) had NRS2002 scores of 1, 2, 3, 4 and 5, respectively. Survival outcomes were comparable between patients with NRS2002 <3 and ≥3 (original scale). However, patients with NRS2002 ≤3 vs >3 (regrouping scale) had significantly different 5‐year disease‐free survival (DFS; 82.7% vs 75.0%, P  <  .001), overall survival (OS; 88.8% vs 84.1%, P = .001), distant metastasis‐free survival (DMFS; 90.2% vs 85.9%, P = .001) and locoregional relapse‐free survival (LRRFS; 91.6% vs 87.2%, P = .001). Therefore, we proposed a revised NRS2002 scale, and found that it provides a better risk stratification than the original or regrouping scales for predicting DFS (area under the curve [AUC] = 0.530 vs 0.554 vs 0.577; P < .05), OS (AUC = 0.534 vs 0.563 vs 0.582; P < .05), DMFS (AUC = 0.531 vs 0.567 vs 0.590; P < .05) and LRRFS (AUC = 0.529 vs 0.542 vs 0.564; P < .05 except scale A vs B). Our proposed NRS2002 scale represents a simple, clinically useful tool for nutritional risk screening in NPC.     

Effects of SMYD3 over-expression on cell cycle acceleration and cell proliferation in MDA-MB-231 human breast cancer cells

Purpose The prognostic significance of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) expression remains unestablished, although EGFR and COX-2 are frequently overexpressed in non-small cell lung cancer (NSCLC). Considering the importance of EGFR activation after ligand binding, however, the expression of phosphorylated EGFR (p-EGFR) may have more significance in predicting tumor aggressiveness in NSCLC than either EGFR or COX-2 expression. Patients and methods We studied the relationships between p-EGFR, EGFR, and COX-2 overexpression and examined their association with prognosis in localized NSCLC. The expression of p-EGFR, EGFR, and COX-2 was studied by immunohistochemistry in 77 surgically-resected stage I/II NSCLC cases. EGFR mutational status was determined by sequencing exons 18–21. Correlation of expression with clinical outcome and other biomarkers, including Ki-67 and microvessel density (MVD), was also examined. Results Out of the 77 patients, EGFR overexpression was observed in 37 (48.1%), p-EGFR expression was found in 22 (28.6%), and COX-2 overexpression was seen in 45 (58.4%). Expression of p-EGFR was associated with COX-2 overexpression (P = 0.047), but not EGFR overexpression or high Ki-67 (P = 0.087 and P = 0.092, respectively). COX-2 overexpression was significantly associated with high Ki-67 (P = 0.011). Expression of p-EGFR correlated with lower disease-free survival (P = 0.045), but not overall survival. Neither EGFR nor COX-2 overexpression was associated with prognosis. Conclusion p-EGFR appears to be a better indicator for lower disease-free survival than EGFR overexpression itself in localized NSCLC. Pathways other than EGFR activation may influence COX-2 overexpression.     

Preoperative chemotherapy is safe in early breast cancer,even after 10 years of follow-up; clinical and translational results from the EORTC trial 10902

Introduction The Preoperative Chemotherapy in Primary Operable Breast Cancer (POCOB) study was designed to compare preoperative with postoperative chemotherapy in patients with early breast cancer concerning breast conserving therapy (BCT) procedures, disease free survival (DFS) and overall survival (OS). Methods Patients (n = 698) with early breast cancer were enrolled between 1991 and 1999 and randomized between preoperative versus postoperative chemotherapy (four cycles of fluorouracil, epirubicin, and cyclophosphamide). Endpoints were BCT procedures, DFS, OS, and tumor response to preoperative chemotherapy. In addition, tumor tissue was collected for translational research and the following markers were examined: ER, PgR, HER2, p21, p53, and bcl-2 expression. Results With a median follow-up of 10 years, there was no statistically significant difference between the two treatment arms for OS (HR = 1.09; 95%CI 0.83–1.42; P = 0.54), DFS (HR = 1.12; 95%CI 0.90–1.39; P = 0.30), or locoregional recurrences (LRR, HR = 1.16; 95%CI 0.77–1.74). Preoperative chemotherapy was associated with an increase in BCT rates. BCT in part feasible due to tumor downsizing after preoperative chemotherapy was not correlated with higher LRR or worse OS compared to BCT which was feasible without downsizing of the tumor. Using available tumor material, only tumor stage, nodal stage, and grade were independent prognostic factors for overall survival. Conclusions Preoperative chemotherapy does not result in a difference in OS or DFS compared to postoperative chemotherapy in patients with early breast cancer. Moreover, it increases BCT rates with no significant increase of LRR. This implies that preoperative chemotherapy is a safe procedure for patients with early breast cancer, even after a follow-up period of 10 years. This article is presented in part as poster and oral presentation at the 5th European Breast Cancer Conference, 21–24 March 2006, Nice, France and 13th Congress of the European Society of Surgical Oncology, 30 November–2 December 2006, Venice, Italy. See appendix for participating institutions and cooperating investigators.     

Simultaneous over activation of EGFR, telomerase (h TERT), and cyclin D1 correlates with advanced disease in larynx squamous cell carcinoma: a tissue microarray analysis

Overexpression of Epidermal Growth Factor Receptor (EGFR) and also of cell cycle control proteins, such as cyclin D1 is a frequent event in squamous cell carcinoma of the larynx (LSSC). Our aim was to correlate their protein levels with telomerase catalytic subunit (h-TERT) expression. Using tissue microarray technology, fifty-five paraffin embedded histologically confirmed primary LSSCs and also ten dysplastic lesions were cored at a diameter of 1.5 mm. Immunohistochemistry (IHC) was performed by the use of anti-EGFR, anti-cyclin D1, and anti-h TERT monoclonal antibodies. Chromogenic in situ hybridization (CISH) analysis was also applied using EGFR gene and chromosome 7 probes, respectively. EGFR, cyclin D1 and h-TERT protein overexpression was observed in 48/55 (87.2%), 19/55 (34.5%) and 21/55 (38.1%) carcinoma cases, respectively. EGFR protein expression was statistically associated with grade (P = 0.01), and also with stage (P = 0.001) of the examined tumors. Borderline statistical significance was assessed correlating overall cyclin D1 expression to h TERT expression (P = 0.06). Simultaneous up regulation of the three proteins was established in 7/55 (12.7%) cases, correlated to the stage of the tumors (P = 0.05). EGFR gene amplification was observed in 7/65 (10.7%) carcinomas and dysplasias, whereas chromosome 7 aneuploidy was detected in 4/65 (6.1%) of those cases.Simultaneous up regulation of EGFR, cyclin D1 and h TERT proteins correlates with advanced stage in LSCC. EGFR gene amplification and not only protein over expression maybe is the eligible criterion for targeted therapeutic strategies in those patients.     

Prognostic value of KRAS mutations and Ki-67 expression in stage I lung adenocarcinomas

The purpose of the present study was to establish accurate prognostic markers to predict the post-operative recurrence of stage I lung adenocarcinomas (ADC). One-hundred and ninety cases of stage I ADC were examined for KRAS mutations and Ki-67 expression, and their associations with disease recurrence were analyzed. KRAS-mutated cases showed a significantly higher risk of recurrence than cases without mutations (5-year disease-free survival (DFS) 61.0% vs. 85.8%, P = 0.017: adjusted Hazard ratio (HR) 4.55, 95% Confidence Interval (CI) 1.61–12.82, P = 0.004). Ki-67 high-expressers (labeling index >10%) also showed a higher risk of recurrence than low-expressers (5-year DFS 68.7% vs. 93.2%, P < 0.001: adjusted HR 3.84, 95% CI 1.18–12.45, P = 0.025). Ki-67 high-expressers with KRAS mutations showed an additional higher risk of recurrence compared to low-expressers without mutations (5-year DFS 37.5% vs. 93.3%, P < 0.001: adjusted HR 16.82, 95% CI 3.77–74.98, P < 0.001) and their 5-year DFS was nearly equivalent to that of stage II non-small cell lung cancer (NSCLC) in our facility (37.5% vs. 37.2% for stage II NSCLC, p = 0.577). The combined use of KRAS status and Ki-67 expression level could be an excellent prognostic marker to predict the post-operative recurrence of stage I ADC.     

Invasive ductal carcinoma of the breast with the “triple-negative” phenotype: prognostic implications of EGFR immunoreactivity

Invasive ductal carcinomas (IDC) of the breast with the triple negative phenotype (steroid hormone receptor absent, negative HER2 status) are characterized by poor clinical outcome. Additional tumor markers might allow identification of patients at higher risk. We evaluated clinical and biological features of 284 consecutive patients with pT1-3, pN1-3 M0 triple-negative IDC. Median follow-up was 70 months (interquartile range 59–94 months). Statistically significant worse disease-free and overall survival were observed in multivariate analysis, for patients with EGFR immunoreactivity in ≥50% invasive tumor cells (HR 2.39, 95% CI, 1.32–4.34, P = 0.004 for DFS; HR 2.34, 95% CI, 1.20–4.59 P = 0.01 for OS). Age ≥ 70 years and PVI were additional independent predictors of reduced overall survival. EGFR immunoreactivity significantly correlates with worse prognosis in patients with triple-negative IDC, supporting further studies on the correlation between the degree of EGFR expression and outcome of triple negative breast cancer.     

EGFR expression correlates with decreased disease-free survival in triple-negative breast cancer: a retrospective analysis based on a tissue microarray

The aim of this study was to analyze the prognostic value of EGFR expression for patients with triple-negative breast cancer (TNBC). Clinical data of these patients were collected and analyzed, and immunohistochemical staining for EGFR was performed on tissue microarrays of operable breast cancer from 287 patients with TNBC, who were treated at Sun Yat-sen University Cancer Center from January 1995 to December 2008. EGFR expression was found in 36.2% of the cases with TNBC. A significant correlation was found between EGFR expression and disease-free survival (DFS). Univariated analysis indicated that EGFR expression had a significant prognostic value in TNBC patients, whereas multivariate analysis indicated that EGFR was a significant independent prognostic factor of DFS (P = 0.011) in all patients. Our results suggested that EGFR was an independent prognostic factor of DFS in patients with TNBC. Therefore, EGFR could become a good therapeutic target in the treatment of TNBC.     

Pneumonectomy in Stage IIIA-N2 NSCLC: Should It Be Considered After Neoadjuvant Chemotherapy?

BackgroundOwing to the expected poor long-term outcomes and high postoperative morbidity and mortality, patients with stage IIIA-N2 tumors candidate to pneumonectomy (PN) are usually excluded from surgery. This study aims to analyze the outcome of patients who underwent PN to prove its safety and feasibility.Patients and MethodsWe retrospectively analyzed data from 233 patients who underwent PN for N2 non–small-cell lung cancer (NSCLC) between 1998 and 2015. Eighty-five patients were occult N2 disease (group 1), whereas 148 patients underwent induction therapy (IT) for stage IIIA-N2 (group 2).ResultsOverall morbidity, postoperative mortality, and 90-day mortality rates were 46.8%, 2.6%, and 8.6%, respectively. The 2 groups (group 1 vs. 2) had similar postoperative and 90-day mortality rates: 2.4% versus 2.7% (P = 1.00), and 9.4% versus 8.1% (P = .81), respectively. The incidence of major morbidity was higher and statistically significant in group 2 compared with group 1: 23% versus 12.9% (P = .1). Postoperative bronchopleural fistula occurred in 4.7% (4/85) of patients with occult N2 (group 1) and in 10.1% (15/148) of patients undergoing IT (group 2) (P = .10). Median overall survival (OS) was 2.2 years, with a 3 and 5-year OS of 43.4% and 31.6%, respectively. Disease-free survival (DFS) was 1.5 years, with 3 and 5-year DFS of 41.6% and 32%, respectively; no difference in OS and DFS between the 2 groups was found.ConclusionsConsidering the acceptable morbidity and mortality rate and the long-term survival, PN should not be excluded for selected patients with stage IIIA-N2 NSCLC as a matter of principle.