Independent Predictor Of Disease-free Survival Research Articles

Insulin-like growth factor II mRNA binding protein 3 expression in the non-muscle invasive bladder cancer and its relationships with the prognosis

Objective To investigate the expression of insulin-like growth factor Ⅱ mRNA binding protein 3 (IMP3) in non-muscle invasive bladder cancer and its relationship with the tumor recurrence and progression. Methods IMP3 protein expression was detected by immunohistochemistry in 130 cases of non-muscle invasive bladder cancer specimens who underwent transurethral resection the first time at Beijing Chao-Yang hospital, from October 2010 to October 2013. Besides, we analyzed 20 cases of muscle-invasive samples and 20 benign tissues adjacent to cancer as control. The 130 patients were followed up by telephone and other methods. According to the UICC-TNM standard.Survival analysis was calculated by using the Kaplan-Meier method, and the difference in survival curves was analyzed by using the log-rank test. For multiple analyses, The Cox proportional hazards regression model was used. Results The positive expression rate of IMP3 in 130 patients with non-muscle invasive bladder cancer was 59.2% (77/130), of which 30.0% (39/130) was weak expression, 29.2% (38/130) was strong. However there was 80.0% (16 /20) in muscle-invasive specimens, of which 20.0% (4/20) was weak, 60.0% (12/20) was strong (P=0.011). IMP3 was not detected in all benign tissues adjacent to cancer (P<0.001). All the 130 patients were followed-up for 5 to 69 months , 45 cases experienced disease recurrence, 20 patients had progressed and 12 cases died.IMP3 expression was significantly related to higher tumor stage (P<0.001), high tumor grade (P=0.014), and tumor recurrence (P=0.003). Kaplan-Meier plots and log-rank tests showed that patients with IMP3-positive tumors had a lower disease-free survival (P=0.002) and progression-free survival rate (P=0.010) than those with IMP3-negative tumors. In the multivariable Cox analysis, we found that IMP3 protein was an independent predictor of disease-free survival (P=0.010) in non-muscle invasive urothelial carcinoma of bladder. Conclusions IMP3 was not expressed in benign tissue adjacent to cancer, whereas highly expressed in bladder cancer, and high IMP3 expression is an independent prognostic factor in NMIBC that can identify the patients with a high potential to relapse. Key words: Insulin-like growth factor Ⅱ mRNA binding protein 3(IMP3); Non-muscle invasive bladder cancer(NMIBC); Prognosis

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Moderately and Poorly Differentiated Appendiceal Adenocarcinoma: Survival Outcomes and Patient Selection.

Moderately and poorly differentiated adenocarcinoma of the appendix represents an aggressive histological variant with a high risk of recurrence and death. Overall, 178 patients with moderately and poorly differentiated appendiceal adenocarcinoma were identified from a prospective database. Clinical, pathologic, and treatment factors were analyzed for outcomes. Diagnostic laparoscopy (DL) identified radiographic occult peritoneal metastasis in 25 (42%) patients. These patients had a significantly lower peritoneal carcinomatosis index (PCI) and improved overall survival (OS) compared with those with radiographic disease. Twenty-seven (41%) patients were excluded from cytoreductive surgery (CRS) because of findings on DL, while 116 (65%) patients underwent CRS and hyperthermic intraperitoneal chemotherapy (HIPEC), with a median disease-free survival (DFS) of 23months. Mucinous histology (hazard ratio [HR] 0.52, p=0.04) and PCI (HR 1.054, p=0.02) were independent predictors of DFS. The median OS following CRS and HIPEC was 48months. Mucinous histology (HR 0.352, p=0.018), signet ring cells (HR 3.34, p=0.02), positive peritoneal cytology (HR 0.081, p=0.04), and PCI (HR 1.076, p=0.004) were independently associated with OS. Eight-five (73.3%) patients received neoadjuvant chemotherapy, and 40 (47.1%) patients achieved a radiographic response; 36 (42.3%) had stable disease, while 9 (10.6%) had progressive disease. Stable or responsive disease was associated with improved median OS of 44months, compared with 21months for those with progressive disease (p=0.011). In selected patients, long-term survival can be obtained. Mucinous histology, absence of signet ring cells, negative peritoneal cytology, PCI≤20, and response/stable disease after neoadjuvant chemotherapy are important selection criteria for CRS and HIPEC.

Impact of persistence on survival of patients with breast cancer treated with endocrine therapy in Northeast China: a prospective study.

The purpose of this prospective study is to investigate the impact of endocrine treatment persistence on the survival of patients with estrogen receptor-positive breast cancer treated with endocrine therapy and identify the risk factors influencing the treatment persistence. We enrolled 1085 patients from Northeast China who were diagnosed as stage I–III, estrogen receptor-positive breast cancer between January 2007 and December 2010. The prognostic factors for disease-free survival (DFS) and overall survival (OS) of patients were identified using univariate and multivariate Cox proportional hazards regression models. Multiple logistic regression analysis was done to determine the possible risk factors for non-endocrine treatment and treatment discontinuation. Among the patients enrolled, 598 (55.1%) underwent 5 years of endocrine therapy, 278 (25.6%) less than 5 years, and 209 (19.3%) non-endocrine therapy. OS rates in the continuation, discontinuation, and non-endocrine treatment groups were 97.8%, 92.6% and 74.3%, and DFS 97.5%, 86.2% and 69.9%, respectively. After adjusting for pathological and socioeconomic factors, non-endocrine therapy and discontinuation were independent predictors for DFS and OS. Elderly patients (≥ 65 years), those living in suburban and rural areas, locally advanced patients, and receiving no radiotherapy and/or chemotherapy were more likely to receive non-endocrine therapy and discontinue endocrine treatment. In conclusion, the prospective study demonstrate that the persistence of endocrine treatment is low in estrogen receptor-positive breast cancer patients in Northeast China. Non-endocrine treatment and early discontinuation serve as independent prognostic factors for both DFS and OS of breast cancer patients treated with endocrine therapy.

Loss of constitutive ABCB1 expression in breast cancer associated with worse prognosis.

ABCB1 gene encodes an adenosine 5′-triphosphate–binding cassette transporter, which not only confers multidrug resistance phenotype in malignant cells, but is also present in several nonmalignant tissues. For the last thirty years, ABCB1 expression in breast cancer has been described by many authors, but the extent of expression differs among the studies, and there is no consensus regarding its potential role in carcinogenesis or in the tumor response to antineoplastic drugs. This study aimed to characterize the expression of ABCB1 in breast tumors as a function of genetic, clinical, and histopathological variables. The ABCB1 expression was also evaluated in nonmalignant mammary tissues adjacent to tumors and in benign lesions. The detection of ABCB1 protein was performed by immunohistochemistry in tissue specimens of excised breasts obtained from a prospective cohort of Brazilian women with breast cancer. The association of ABCB1 protein levels with ABCB1 mRNA, gene polymorphisms, and clinical and histopathological variables was also evaluated. The Kaplan–Meier curves and multivariate Cox regression analyses were conducted to identify independent predictors of disease-free survival of patients with breast cancer. ABCB1 was detected in 86.3% (656) of breast tumors, 98.8% (606) of nonmalignant mammary tissue adjacent to tumors, and 100% (28) of benign lesions. Reduced ABCB1 protein levels in breast tumors was associated with triple-negative subtype (adjusted odds ratio [ORadj] =0.24; 95% confidence interval [CI] =0.13–0.45), lymph node status < pN2 (ORadj =0.27; 95% CI =0.10–0.71), tumor size >2 cm (ORadj =0.55; 95% CI =0.32–0.93), and hypertensive status (ORadj =0.42; 95% CI =0.24–0.73), and it was significantly associated with shorter disease-free survival, either for all breast cancer patients (p log-rank =0.012; hazard ratio [HR] =3.46; 95% CI =1.21–9.91) or for those with triple-negative tumors (p log-rank =0.007; HR =11.41; 95% CI =1.29–100.67). The loss of constitutive ABCB1 expression in breast cancer, especially in triple-negative tumors, seems to indicate a subgroup of worse prognosis.

Pretreatment albumin level predicts survival in head and neck squamous cell carcinoma.

Poor nutritional status in patients with head and neck squamous cell carcinoma (HNSCC) is associated with tumor progression and survival. This study examined the prognostic value of nutritional and hematological markers in patients with HNSCC who received definitive treatments. A prospective observational cohort study. This study included 338 consecutive patients who underwent surgery and/or radiotherapy/chemoradiotherapy for treatment-naïve HNSCC. Body weight and nutritional and hematological parameters were regularly measured before and after treatment. Univariate and multivariate analyses using Cox proportional hazards models were performed to identify factors associated with disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS). Body weight, serum total protein and albumin levels, and hematological variables significantly decreased after treatment. Univariate analyses illustrated that age, tumor site, T and N classifications, overall stage, pretreatment serum albumin (<3.5 g/dL) and hemoglobin (<12 g/dL) levels, and neutrophil-lymphocyte ratio were significantly associated with DFS, CSS, and OS (all P < .05). Multivariate analyses identified age, tumor site, N classification, and pretreatment albumin levels as independent predictors of DFS, CSS, and OS (all P < .05). Patients with low serum albumin levels prior to treatment experienced approximately sixfold increases in the risks of tumor progression and cancer-specific and overall mortality compared to the findings in their counterparts. Our results suggest that pretreatment serum albumin levels predict DFS, CSS, and OS in patients who received definitive treatment for HNSCC. These findings might help to predict treatment outcome and guide nutritional intervention in patients with HNSCC. 2b. Laryngoscope, 127:E437-E442, 2017.

Long-term outcomes of 307 patients after complete thymoma resection

BackgroundThymoma is an uncommon tumor without a widely accepted standard care to date. We aimed to investigate the clinicopathologic variables of patients with thymoma and identify possible predictors of survival and recurrence after initial resection.MethodsWe retrospectively selected 307 patients with thymoma who underwent complete resection at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China) between January 2003 and December 2014. The associations of patients’ clinical characteristics with prognosis were estimated using Cox regression and Kaplan–Meier survival analyses.ResultsDuring follow-up (median, 86 months; range, 24–160 months), the 5- and 10-year disease-free survival (DFS) rates were 84.0% and 73.0%, respectively, and the 5- and 10-year overall survival (OS) rates were 91.0% and 74.0%, respectively. Masaoka stage (P < 0.001), World Health Organization (WHO) histological classification (P < 0.001), and postoperative radiotherapy after initial resection (P = 0.006) were associated with recurrence (52/307, 16.9%). Multivariate analysis revealed that, after initial resection, WHO histological classification and Masaoka stage were independent predictors of DFS and OS. The pleura (25/52, 48.0%) were the most common site of recurrence, and locoregional recurrence (41/52, 79.0%) was the most common recurrence pattern. The recurrence pattern was an independent predictor of post-recurrence survival. Patients with recurrent thymoma who underwent repeated resection had increased post-recurrence survival rates compared with those who underwent therapies other than surgery (P = 0.017).ConclusionsMasaoka stage and WHO histological classification were independent prognostic factors of thymoma after initial complete resection. The recurrence pattern was an independent predictor of post-recurrence survival. Locoregional recurrence and repeated resection of the recurrent tumor were associated with favorable prognosis.

Surgical outcomes of pulmonary mucoepidermoid carcinoma: A review of 41 cases.

IntroductionPulmonary mucoepidermoid carcinoma is a rare cancer that occurs primarily in younger patients. The prognostic factors of pulmonary mucoepidermoid carcinoma are largely undetermined, especially in elderly patients. The aim of this study was to examine the clinical characteristics and prognostic factors influencing survival after surgical resection in patients with pulmonary mucoepidermoid carcinoma and also analyze the clinical manifestations and prognostic factors in elderly patients.Materials and methodsThe pathological records of 41 pulmonary mucoepidermoid carcinoma patients (mean age, 61.4 years) who underwent surgical resection at our hospital between January 1991 and July 2015 were retrospectively reviewed. Subjects >65 years of age (n = 22) were considered elderly.ResultsThe median follow-up duration was 42.9 (interquartile range, 15.0–120.8) months. Sixteen patients (39.0%) experienced tumor relapse, including 13 patients (81.3%) within 2 years. The 5-year disease-free survival rate was 57.9%. Tumor grade did not influence disease-free survival (P = 0.286). In the multivariate analysis, age, tumor size, pathological T3–4 status, and pathological N2 status were independent predictors of disease-free survival. The 5-year overall survival rate was 57.0%. Tumor grade also did not influence overall survival (P = 0.170). Age, tumor size, pathological T status, and pathological N2 status were independent predictors of overall survival. In elderly patients, the 5-year disease-free survival and overall survival rates were 41.4% and 41.5%, respectively. Pathological T status was the only independent predictor of both disease-free survival and overall survival in elderly patients.ConclusionsPrognostic factors identified for pulmonary mucoepidermoid carcinoma in this study differ from those of previous studies. Principally, tumor grade did not influence either disease-free survival or overall survival. Age, tumor size, and pathological factors were independent predictors of disease-free survival and overall survival. In elderly patients, pathological T status was the only independent predictor of disease-free survival and overall survival.

Comparison of clinical features and survival between thymic carcinoma and thymic carcinoid patients.

Thymic carcinoma (TC) and thymic carcinoid (TCD) are aggressive thymic epithelial neoplasms with a poor prognosis. Due to rarity, little is known about their comparative clinical characteristics, treatment outcomes and patterns of relapse. A retrospective cohort study was performed on 287 patients with TC and 56 patients with TCD who were treated at the Shanghai Chest Hospital between February 2003 and April 2014. Patient demographics, tumour stage, treatment, pathologic findings and postoperative outcomes were compared between the two tumour types using both multivariable Cox regression analysis and propensity-matched analysis. Compared to patients with TC, significantly more patients with TCD were male, had larger tumours, and displayed a greater proportion of lymph node metastases. However, overall survival was similar (60.7% 5-year survival for TC, 80.7% for TCD, P = 0.159), as was disease-free survival (41.1% 5-year survival for TC, 37.6% for TCD, P = 0.696) and patterns of relapse. Multiple Cox regression analysis identified younger patients [hazard ratio (HR) 1.018; 95% confidence interval (CI) 1.000-1.035; P = 0.047], more completeness of resection (HR 1.424; 95% CI 1.105-1.836; P = 0.006), adjuvant radiotherapy (HR 0.455; 95% CI 0.276-0.751; P = 0.002), and no adjuvant chemotherapy (HR 1.799; 95% CI 1.017-3.183; P = 0.044) as independent factors predicting better overall survival. Completeness of resection (HR 1.258; 95% CI 1.022-1.548; P = 0.031) and TNM stage (HR 1.479; 95% CI 1.107-1.977; P = 0.008) were independent predictors of disease-free survival. Propensity matching produced 46 patients in each group and no significant difference on overall survival or disease-free survival was found. Patients with TCD have discrete features but share a similar clinical course to those with TC. The importance of complete resection in both of these thymic malignancies is emphasized. Further investigation at multiple centers with the longer follow-up data is required to substantiate our conclusion.

A semi-quantitative World Health Organization grading scheme evaluating worst tumor differentiation predicts disease-free survival in oral squamous carcinoma patients.

We investigated World Health Organization (WHO) grading and pattern of invasion based histological schemes as independent predictors of disease-free survival, in oral squamous carcinoma patients. Tumor resection slides of eighty-seven oral squamous carcinoma patients [pTNM: I&II/III&IV-32/55] were evaluated. Besides examining various patterns of invasion, invasive front grade, predominant and worst (highest) WHO grade were recorded. For worst WHO grading, poor-undifferentiated component was estimated semi-quantitatively at advancing tumor edge (invasive growth front) in histology sections. Tumor recurrence was observed in 31 (35.6%) cases. The 2-year disease-free survival was 47% [Median: 656; follow-up: 14-1450] days. Using receiver operating characteristic curves, we defined poor-undifferentiated component exceeding 5% of tumor as the cutoff to assign an oral squamous carcinoma as grade-3, when following worst WHO grading. Kaplan-Meier curves for disease-free survival revealed prognostic association with nodal involvement, tumor size, worst WHO grading; most common pattern of invasion and invasive pattern grading score (sum of two most predominant patterns of invasion). In further multivariate analysis, tumor size (>2.5cm) and worst WHO grading (grade-3 tumors) independently predicted reduced disease-free survival [HR, 2.85; P=0.028 and HR, 3.37; P=0.031 respectively]. The inter-observer agreement was moderate for observers who semi-quantitatively estimated percentage of poor-undifferentiated morphology in oral squamous carcinomas. Our results support the value of semi-quantitative method to assign tumors as grade-3 with worst WHO grading for predicting reduced disease-free survival. Despite limitations, of the various histological tumor stratification schemes, WHO grading holds adjunctive value for its prognostic role, ease and universal familiarity.

Expression of EMT markers and mode of surgery are prognostic in phyllodes tumors of the breast.

Phyllodes tumors of the breast are rare neoplasms that account for <1% of all mammary tumors and 2-3% of fibro-epithelial neoplasms of the breast. We evaluated the clinicopathological characteristics of a cohort of 246 Chinese patients in relation to the expression of epithelial-to-mesenchymal (EMT) markers in benign, borderline and malignant tumors and the prognostic value of different surgical regimens. We observed that survival outcomes correlated with the mode of surgical management in the three patient groups. Expression of E-cadherin, Snail, Slug and Twist were higher in epithelial cells from borderline and malignant tumors than those in benign tumors, whereas the expression of N-cadherin was opposite. Levels of the EMT markers Snail and Slug in the stromal compartment increased with the advancing tumor grade. Expression of mesenchymal stem cell markers contributed to the inherent heterogeneity in the malignant tumors. Based on Cox models, surgical management emerged as an independent predictor for disease-free survival, whereas a history of recent growth and tumor grade were independent predictors for overall survival. These findings show that expression of EMT markers, the mode of surgical management, and a history of recent tumor growth had prognostic potential for patients with phyllodes tumors of the breast.

Prognosis and Progression of ESCC Patients with Perineural Invasion

Perineural invasion (PNI) has been recognized as a poor prognostic factor in several malignancies, but the definition and pathogenesis of PNI in esophageal squamous cell carcinoma (ESCC) remains to be defined. PNI was evaluated by H&E staining and S100 immunohistochemistry. The predictive value of PNI in the prognosis of ESCC patients was analyzed. PNI was evaluated in vitro and in vivo. A total of 54 specimens (17.88%) were defined as PNI-a and 99 specimens (32.78%) as PNI-b. S100 staining was superior to H&E staining for PNI detection (50.66% vs 27.15%, P < 0.001, κ = 0.506). Tumor depth (P = 0.001), tumor stage (P = 0.010), and vascular invasion (P < 0.001) were significantly associated with PNI. PIN-a and PNI-b had significant lower disease free survival (DFS) and disease specific survival (DSS) than PNI-0 patients, and the prognosis of PNI-b patients was significantly worse than PNI-a patients for DFS (P = 0.009). PNI was an independent predictor for DFS and DSS in ESCC as evaluated by univariate and multivariate analyses. ESCC cells could metastasize along the nerve in vitro and in vivo, and PNI was a dynamic process. S100 staining significantly improved the accuracy of PNI detection. PNI was associated with local recurrence and poor prognosis of ESCC patients.

Prognostic values of apoptosis-stimulating P53-binding protein 1 and 2 and their relationships with clinical characteristics of esophageal squamous cell carcinoma patients: a retrospective study

BackgroundEsophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related death, and new prognostic biomarkers are urgently needed. Apoptosis-stimulating P53-binding protein 1 (ASPP1) and 2 (ASPP2) have been reported to play important roles in the development, progression, metastasis, and prognosis of cancers, but their roles in ESCC have not been elucidated. In this study, we examined the expression of ASPP1 and ASPP2 in ESCC to evaluate their prognostic values.MethodsThe protein expression of ASPP1, ASPP2, and P53 in 175 specimens of ESCC was detected using immunohistochemical staining; their expression in cancerous and noncancerous tissues was scored according to the staining intensity and the percentage of stained cells. The associations of ASPP1, ASPP2, and P53 with clinicopathologic parameters, overall survival (OS), and disease-free survival (DFS) were analyzed.ResultsThe protein expression levels of ASPP2 and P53 were significantly higher in cancerous tissues than in paired noncancerous tissues (P < 0.001), whereas the expression levels of ASPP1 in the two groups were similar. In ESCCs, ASPP1 expression was significantly associated with histological differentiation (P = 0.002) and invasive depth (P = 0.014); ASPP2 expression was associated with age (P = 0.029) and histological differentiation (P < 0.001); and P53 expression was associated with age (P = 0.021) and tumor size (P = 0.040). No correlations were found between ASPP1, ASPP2, and P53 expression. Survival analysis revealed that high ASPP2 expression was significantly associated with increased 5-year OS (P = 0.001) and DFS rates (P = 0.010) and that high P53 expression was significantly associated with a reduced 5-year DFS rate of ESCC patients (P = 0.015). Multivariate Cox analysis indicated that ASPP2 was an independent predictor of OS [hazard ratio (HR): 0.541, 95% confidence interval (CI) 0.363–0.804] and DFS (HR: 0.599, 95% CI 0.404–0.888) of ESCC patients and that P53 was an independent predictor of DFS (HR: 2.161, 95% CI 1.100–4.245).ConclusionsASPP1 might be involved in the progression of ESCC, and ASPP2 was a potential prognostic biomarker of ESCC and should be evaluated in future studies.

Clinical significance and prognostic value of SOX7 expression in liver and pancreatic carcinoma.

Sex determining region Y-box 7 (SOX7) is known to function as a tumor suppressor in a number of types of cancer; however, its role in liver and pancreatic carcinoma remains unclear. The present study investigated the association between SOX7 expression and the clinical pathology of these carcinomas, in particular if SOX7 expression may be used to predict recurrence and patient prognosis following radical resection of liver and pancreatic carcinoma. SOX7 expression in human liver and pancreatic carcinoma was detected by immunohistochemical analyses and validated using mRNA data from a high-throughput sequencing dataset from The Cancer Genome Atlas (TCGA). SOX7 expression was significantly downregulated in liver and pancreatic carcinoma relative to the adjacent benign tissues [immunoreactivity scores: Liver carcinoma (3.53±1.57) vs. benign (7.00±0.00), P<0.001; and pancreatic carcinoma (2.39±1.88) vs. benign (4.80±0.45), P=0.005]. In addition, downregulation of SOX7 was significantly associated with advanced stage liver carcinoma, and the primary pathological tumor stage and regional lymph node stages. These findings were further validated in the TCGA dataset. However, SOX7 down regulation was closely associated with the only pathological grade in pancreatic patients. Kaplan-Meier analyses revealed significant differences in overall and disease-free survival between patients with high and low levels of SOX7 expression. In addition, a multivariate analysis with Cox regression indicated that SOX7 may be an independent predictor of disease-free survival. The results indicate that SOX7 may inhibit the progression of liver carcinoma and that SOX7 downregulation may accurately predict poor prognosis in liver carcinoma patients.

Patterns and Predictors of Recurrence after Partial Nephrectomy for Kidney Tumors

We sought to identify patterns and predictors of recurrence in patients with clinically localized renal cell carcinoma managed by partial nephrectomy. We performed a retrospective study of 830 consecutive cases of partial nephrectomy done between 2007 and 2015 for clinically localized renal cell carcinoma at a single institution. Patient demographics and pathological characteristics were correlated with recurrence patterns (overall, local and distant) and overall survival using Kaplan-Meier and Cox regression analyses. Differences in the recurrence patterns were evaluated. Median patient age was 61 years and median tumor size was 3.1 cm. Overall, 11.6% of tumors were stage pT3, 39.3% were high grade, 2.9% had lymphovascular invasion and 7.1% had positive margins. Higher grade, higher stage, positive surgical margins and increased R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of deepest tumor portion to collecting system or sinus, anterior/posterior and location relative to polar line) score were associated with shorter disease-free survival on Kaplan-Meier analysis. On multivariable regression pT (p <0.01), grade (p <0.01) and R.E.N.A.L. score (p = 0.03) remained independent predictors of disease-free survival. Predictors of metastasis were pT stage (HR 4.5) and grade (HR 3.9, both p <0.01), while R.E.N.A.L. score (HR 3.2, p = 0.03) was the single predictor of local recurrence. Five-year disease-free and overall survival probabilities were 91% and 94%, respectively. Local recurrence manifested and developed earlier than metastasis (median 13 vs 22 months, p<0.01). High pT stage, high grade and high R.E.N.A.L. score increase the risk of disease recurrence after partial nephrectomy. The pT stage and grade are predictors of metastasis, while R.E.N.A.L. score predicts local recurrence. Because relapse features and risk factors differ between the 2 recurrence patterns, they should be studied separately in the future.

Pancreatic adenocarcinoma up-regulated factor has oncogenic functions in oral squamous cell carcinoma.

Pancreatic adenocarcinoma up-regulated factor (PAUF) is a novel secretory protein which promotes tumour progression, metastasis and poor prognosis in pancreatic, cervical and colorectal carcinoma. It is also associated with gemcitabine resistance in pancreatic cancer cells. However, the expression and function of PAUF in oral squamous cell carcinoma (OSCC) remain unknown. We performed an immunohistochemical analysis of PAUF in 222 clinicopathologically characterized cases of OSCC. We also investigated the growth, invasion, apoptosis induction and cisplatin resistance of OSCC cells under PAUF knockdown treatment. PAUF was localized in normal salivary glands. In OSCC, immunostaining for PAUF was found in 52 of 222 patients (23.4%), and correlated with nodal metastasis (P < 0.0001) and poor prognosis (P < 0.0001). Multivariate analysis using the Cox proportional hazards model identified that PAUF expression was an independent predictor of disease-free survival in OSCC (P < 0.0001). The down-regulation of PAUF in OSCC cells suppressed cell growth and invasion and induced apoptosis and cisplatin sensitivity. Our results suggest that PAUF has tumour-promoting functions in OSCC. It may thus be a useful diagnostic and therapeutic marker for OSCC.

Primary Breast Angiosarcoma: A Retrospective Study of 36 Cases from a Single Chinese Medical Institute with Clinicopathologic and Radiologic Correlations.

The aim of this study was to present our experience with primary breast angiosarcoma (PBA) by describing a large series of cases with an emphasis on clinicopathologic and radiologic correlations. Thirty-six cases of PBA diagnosed at our institution between 2006 and 2014 were retrospectively evaluated. All but one case occurred in women with a median age of 35.5 years. The majority of patients presented with a deeply located painless mass, whereas a minority manifested as diffuse enlargement or swelling of the breast. Magnetic resonance imaging showed poorly demarcated lesions with low signal intensity on T1-weighted images, markedly high intensity on T2-weighted images, and prolongation of enhancement upon dynamic study. Histologically, 19 cases (52.8%) were low grade, 12 cases (33.3%) were intermediate grade, and 5 cases (13.9%) were high grade. Follow-up information was available for 27 patients and revealed local recurrence and/or metastasis in 16 patients (59.3%). Five patients (18.5%) died of the disease at a median interval of 20 months. Univariate analysis showed that tumor differentiation had effect on disease-free survival (DFS) (p = 0.005) but failed to predict overall survival (OS) (p = 0.645). The treatment modality was related to OS (p = 0.042) but not DFS (p = 0.131). The Cox proportional hazards regression model suggested that tumor differentiation was an independent predictor of DFS (p = 0.015). We hypothesize that tumor differentiation may be used as a prognostic factor for this rare malignancy. Clinicopathologic and radiologic correlation may help pathologists to arrive at the correct diagnosis of PBA.

Does the TNM classification of solitary internal mammary lymph node metastases in breast cancer still apply?

PurposeTNM classification of solitary internal mammary lymph node metastases (IMLNMs) in breast cancer varies depending on their method of detection: sentinel lymph node biopsy (pN1b) or clinical examination including radiological and/or physical examination (pN2b). This study aimed to evaluate whether there is a difference in prognosis between both groups.MethodsData of all patients diagnosed with primary invasive epithelial breast cancer between 2005 and 2008 were obtained from the Netherlands Cancer Registry. Patients with IMLNMs were divided in groups according to their pN1b and pN2b status. The main outcome measures disease-free survival (DFS) after 5 years and overall survival (OS) after 8 years were analyzed using Kaplan–Meier survival analysis. Cox regression analysis was used to determine independent predictors for DFS and OS.ResultsA total of 73 patients with pN1b status and 28 patients with pN2b status were included. DFS rate was 74.1% in the pN1b group compared to 85.0% in the pN2b group (p = 0.211). Regarding OS, 20.5% (pN1b) and 25.0% (pN2b) of the patients deceased within 8 years of follow-up (p = 0.589). In multivariable cox regression analysis, nodal status was not statistically significant for DFS (HR 0.29 [95% CI 0.04–2.33], p = 0.244) or OS (HR 1.04 [95% CI 0.37–2.89], p = 0.947).ConclusionsAlthough the TNM classification considers pN1b and pN2b to be distinct prognostic entities, we did not observe any prognostic differences between these groups. Therefore, solitary IMLNMs may be regarded as a single category in the future and revision of TNM classification should be considered.

Diffusion-Weighted Magnetic Resonance Imaging as a Predictor of Outcome in Cervical Cancer After Chemoradiation

Todetermine whether apparent diffusion coefficient (ADC) value is predictive of survival after definitive chemoradiation for cervical cancer independent of established imaging and clinical prognostic factors. Between 2011 and 2013, the pretreatment MRI scans for 69 patients treated with definitive chemoradiation for newly diagnosed cervical cancer were retrieved. Scans were acquired with a 1.5-T magnetic resonance scanner, including diffusion-weighted imaging sequences. Mean ADC value was measured within a region of interest in the primary cervical cancer on the baseline MRI scan. Baseline tumor maximum standardized uptake value on positron emission tomography/computed tomography was determined by the reading radiologist. Treatment included external beam radiation therapy to the pelvis followed by brachytherapy in 97%, and with concurrent weekly cisplatin in 99% of patients. Univariate and multivariate analyses were done to investigate the association of clinical and imaging variables with disease control and survival endpoints using a Cox proportional hazard test. Median follow-up was 16.7months (range, 3.1-44.2months). The 1-year overall survival, locoregional recurrence-free survival, and disease-free survival rates were 91%, 86%, and 74%, respectively. The median ADC value was 0.941×10-3mm2/s (range, 0.256-1.508×10-3mm2/s). The median standardized uptake value in the primary tumor was 15 (range, 6.2-43.4). In multivariate analysis, higher ADC value (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.15-0.85, P=.02), higher stage (HR 2.4, 95% CI 1.1-5.5, P=.033), and nonsquamous histology (HR 0.23, 95% CI 0.07-0.82, P=.024) were independent predictors of disease-free survival. The mean ADC value of the primary tumor on pretreatment MRI was the only imaging feature that was an independent predictor of disease-free survival in cervical cancer patients treated with chemoradiation. Further validation will be needed to determine whether ADC values may prove useful in identifying cervical patients at high risk of recurrence.

Programmed Death-Ligand 1 Expression Is Common in Gastric Cancer Associated With Epstein-Barr Virus or Microsatellite Instability

Blockade of the programmed death 1 (PD-1) pathway has emerged as a novel therapy for cancer. Therefore, development of biomarkers for response prediction, such as PD-ligand 1 (PD-L1) expression by immunohistochemistry, may help to stratify patients. Solid tumors with CD8 T-cell rich tumor microenvironment have been implicated to be associated with increased PD-L1 expression. We hypothesized that gastric cancers associated with Epstein-Barr virus infection (EBV+) or microsatellite instability (MSI), both of which are known to harbor such tumor microenvironment, are associated with increased PD-L1 expression. Forty-four resected gastric cancers including 7 EBV+, 16 MSI, and 21 microsatellite stable cancers without EBV (EBV-/MSS) were studied for PD-L1 expression and T-cell subpopulations by immunohistochemistry. Positive PD-L1 expression (PD-L1+), defined as membranous staining in either tumor cells or tumor immune infiltrates, was seen in 32 (72%) gastric cancers. EBV+ or MSI cancers showed significantly higher rates of PD-L1+ compared with EBV-/MSS cancers (7/7, 100%; 14/16, 87%; 11/21, 52%; P=0.013). PD-L1+/EBV+ and PD-L1+/MSI cancers had significantly more CD8 T cells at tumor invasive front than PD-L1+/EBV-/MSS cancers (P<0.001). PD-L1+ was not associated with the depth of invasion or nodal metastasis (P=0.534, 0.288). Multivariate analysis showed PD-L1+ was not an independent predictor of disease-free survival while MSI was (P=0.548, 0.043). In summary, EBV+ or MSI gastric cancers are more likely to express PD-L1 and have increased CD8 T cells at tumor invasive front than EBV-/MSS cancers. Our results suggest EBV infection and MSI should be investigated for predicting response to PD-1 blockade.

The postoperative neutrophil-to-lymphocyte ratio and changes in this ratio predict survival after the complete resection of stage I non-small cell lung cancer.

PurposeAlthough numerous studies have demonstrated associations between the preoperative neutrophil-to-lymphocyte ratio (NLR) and long-term outcomes in patients with non-small cell lung cancer (NSCLC), the prognostic significance of postoperative NLR and change in NLR (ΔNLR) is unknown for patients who underwent complete resection of stage I NSCLC. The aim of this retrospective study was to evaluate the prognostic significance of postoperative NLR and ΔNLR in 123 patients with stage I NSCLC.Patients and methodsThis retrospective study included preoperative and postoperative data of 123 patients who underwent surgical resection for stage I NSCLC. The relationship between disease-free survival (DFS), overall survival (OS), and clinicopathological factors, including NLR, lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio, and their changes, was analyzed using both univariate Kaplan–Meier and multivariate Cox regression methods.ResultsThe 5-year DFS and OS rates in our cohort were 60.16% and 67.48%, respectively. Univariate analysis revealed that age (P=0.045), smoking status (P=0.033), preoperative NLR (P=0.032), postoperative NLR (P<0.001), ΔNLR (P=0.004), and change in LMR (ΔLMR) (P=0.025) were significant predictors of DFS and that age (P=0.039), smoking status (P=0.042), postoperative NLR (P<0.001), ΔNLR (P=0.004), and ΔLMR (P=0.011) were independent predictors of OS. Multivariate analysis confirmed that postoperative NLR (hazard ratio [HR] =2.435, P=0.001) and ΔNLR (HR =2.103, P=0.012) were independent predictors of DFS and that postoperative NLR (HR =2.747, P=0.001) and ΔNLR (HR =2.052, P=0.018) were significant prognostic factors of OS.ConclusionOur study reported for the first time that postoperative NLR and ΔNLR – but not preoperative NLR – were independent prognostic factors of DFS and OS in patients with stage I NSCLC who underwent complete resection. This easily available biomarker might be helpful in individual risk assessment.