Clinical outcomes of children and adults with central nervous system primitive neuroectodermal tumor

Central nervous system primitive neuroectodermal tumors (CNS PNETs) predominantly occur in children and rarely in adults. Because of the rarity of this tumor, its outcomes and prognostic variables are not well characterized. The purpose of this study was to evaluate clinical outcomes and prognostic factors for children and adults with CNS PNET. The records of 26 patients (11 children and 15 adults) with CNS PNET from 1991 to 2011 were reviewed retrospectively. Disease-free survival (DFS) and overall survival (OS) were estimated with the Kaplan–Meier method, and relevant prognostic factors were analyzed. For the cohort, both the 5-year DFS and the OS were 46 %. For pediatric patients, the 5-year DFS was 78 %; for adult patients, it was 22 % (P = 0.004). Five-year OS for the pediatric and adult patients was 67 and 33 %, respectively (P = 0.07). With bivariate analysis including chemotherapy regimen (high dose vs. standard vs. nonstandard) or risk stratification (standard vs. high) and age, the increased risk of disease recurrence in adults persisted. A nonsignificant tendency toward poorer OS in adult patients relative to pediatric patients also persisted. High-dose chemotherapy with stem cell rescue was associated with a statistically significant improvement in OS and a tendency toward improved DFS, although the findings were mitigated when the effect of age was considered. Local recurrence was the primary pattern of treatment failure in both adults and children. Our results suggest that adult patients with CNS PNETs have inferior outcomes relative to the pediatric cohort. Further research is needed to improve outcomes for CNS PNET in populations of all ages.     

Evaluation of osteopontin as a potential biomarker for central nervous system embryonal tumors

Osteopontin (OPN) is a protein linked to tumor growth, progression and metastasis of cancers. However, its role in the progression of central nervous system (CNS) embryonal tumors such as atypical teratoid/rhabdoid tumor (AT/RT), medulloblastoma (MB) and primitive neuroepithelial tumors (PNET) remains elusive. In this study, we investigated the value of OPN staining in differential diagnosis of AT/RT from MB and PNET, and assessed the correlation between OPN expression and patients’ prognosis. This retrospective study was conducted on tissue sections obtained from children cases with CNS embryonal tumors treated in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from 2006 to 2012 by immunohistochemistry (IHC). 49 cases were collected (11 AT/RTs, 25 MBs, and 13 PNETs), with a median follow-up time of 28.9 months. OPN expression in AT/RT was significantly higher than MB and PNET with the positive rates of 100, 32, and 23 %, respectively (P < 0.01). The specificity and sensitivity of OPN staining in diagnosing AT/RT are 97.4 and 90.9 %, respectively, as judged by strong OPN IHC staining level (+++). Patients who had positive OPN staining have increased risks of poorer median overall survival (hazard risk 5.54, 95 % CI 1.87–16.38) and tumor progression (hazard risk 14.47, 95 % CI 4.47–46.85). OPN is a valuable biomarker to aid in the differential diagnosis between AT/RT and MB/PNET. Moreover, OPN is a potential novel prognostic marker for CNS embryonal tumors.     

Patterns of care in adult medulloblastoma: results of an international online survey

The literature on medulloblastoma in adults is generally limited to case reports and retrospective series, and there is no accepted standard of care. The Cooperative Trials Group for Neuro-Oncology (COGNO) sought to determine the range and consistency of clinicians’ approaches to management as a basis for future trials. We aimed to identify current treatment strategies for adult medulloblastoma through an online survey launched at the 2012 Society of Neuro-Oncology meeting and by email invitation. Clinicians who had treated at least one adult patient with medulloblastoma, primitive neuroectodermal tumor (PNET), or pineoblastoma in the preceding year were asked about their most recent patient and invited to discuss their approach to a typical clinical scenario. Between November 2012 and January 2013, 45 clinicians (11 medical oncologists, 8 radiation oncologists, 5 pediatric oncologists, and 21 others) from Australia (24), United States (3), Europe (4) and other countries (14) completed the survey. Responding clinicians had treated 54 cases in the past 12 months. The most common histological type was medulloblastoma (64 %), then PNET (20 %). Most patients were male (68 %), and had high-risk disease (65 %). Complete surgical resection in 56 and 32 % had molecular testing. Radiotherapy was predominantly cranio-spinal (92 %) and given mostly post-resection (80 %). Combination chemotherapy was more common than single-agent chemotherapy. The choice of chemotherapy varied considerably. There is substantial variation in the treatment of adult medulloblastoma, most pronounced in the choice of chemotherapeutic agents, highlighting the need for further collaborative research to guide evidence-based treatment strategies.     

The diagnostic,predictive, and prognostic role of serum epithelial cell adhesion molecule (EpCAM) and vascular cell adhesion molecule-1 (VCAM-1) levels in breast cancer

The purpose of this study was to determine the clinical significance of vascular cell adhesion molecule-1 (VCAM-1) and epithelial cell adhesion molecule (EpCAM) in breast cancer (BC) patients. Ninety-six BC patients and 30 age- and sex-matched healthy controls were enrolled into this study. Pretreatment serum markers were determined by the solid-phase sandwich (enzyme-linked immunosorbent assay (ELISA)). The median age at diagnosis was 48 years (range 29–80 years). Majority of the patients (71 %) had luminal subtype, and 38.5 % had metastatic disease. Twenty-nine (30 %) patients showed tumor progression, and 20 (21 %) patients died during follow-up. Median progression-free survival (PFS) and overall survival (OS) were 8.6?±?1.7 and 35.5?±?1.5 months, respectively. The baseline serum EpCAM levels of the patients were significantly higher than those of the controls (p?VCAM-1 between the patients and controls (p?=?0.47). No significant correlation was detected between the levels of the serum markers and other clinical parameters (p?>?0.05). Patients with HER-2-positive and triple-negative tumors had significantly poorer PFS (p?=?0.04 and p?=?0.001, respectively), while metastatic disease and chemotherapy unresponsiveness had significantly adverse effect on OS analysis (p?p?VCAM-1 levels nor serum EpCAM levels were identified to have a prognostic role on either PFS or OS (VCAM-1 p?=?0.76 and p?=?0.32; EpCAM p?=?0.16 and p?=?0.69, respectively). Even though any predictive or prognostic role could not be determined for both markers, serum levels of EpCAM were found to have diagnostic value in BC patients.     

Long progression-free survival with first-line paclitaxel plus platinum is associated with improved response and progression-free survival with second-line docetaxel in advanced non-small-cell lung cancer

Purpose

Paclitaxel and docetaxel are two taxanes approved for the treatment of non-small-cell lung cancer (NSCLC). However, there is limited evidence regarding the efficacy of docetaxel in NSCLC previously treated with a paclitaxel–platinum doublet (PP). The aim of our study was to evaluate the response to docetaxel in NSCLC patients with prior PP treatment.

Methods

Patients with stage IV NSCLC treated with PP that presented disease progression and received docetaxel as second-line treatment were included. Demographics, clinical characteristics, EGFR mutation status, objective response (OR), overall survival (OS), progression-free survival (PFS), and PFS without chemotherapy after first line with PP were analyzed.

Results

Sixty-three patients were evaluated. Median age was 58 years, 54 % of patients were women, 53 % were never-smokers, and 39 % had EGFR mutations. OR and median PFS for PP were 36.5 % and 6.7 months, respectively. OR and median PFS for docetaxel were 19 % and 3.8 months, respectively. Patients with EGFR mutations had better response to docetaxel compared with wild-type patients (26 vs. 17 %, p = 0.028). However, only long PFS (>6 months) to first-line PP was independently associated with a higher OR [RR 6.3, 95 % CI (1.03–38.4), p = 0.046], and longer PFS [0.49 (0.25–0.9)] and OS [0.2 (0.06–0.7), p = 0.008] to second-line docetaxel compared with patients with short PFS (≤6 months) to PP.

Conclusions

Previous use of PP does not preclude a favorable response to docetaxel in NSCLC. Long PFS with PP may help select NSCLC patients who benefit from second-line docetaxel.     

Risk and outcomes of chemotherapy-induced diarrhea (CID) among patients with colorectal cancer receiving multi-cycle chemotherapy

Background

Diarrhea is a common toxicity of chemotherapy, but the practice of reporting only severe grades (≥ 3) in clinical trials results in misleading conclusions of significance. Epidemiology remains poorly described, and effects of multi-cycle regimens have not been investigated. To better understand the risks, symptom burden and consequences of CID, we studied patients receiving chemotherapy for colorectal cancer (CRC).

Methods

One hundred and fourteen patients receiving FOLFOX (95 patients, 530 cycles), FOLFOX + monoclonal antibodies (10 patients, 49 cycles) or FOLFIRI (9 patients, 50 cycles) were enrolled. CID was identified from diaries at baseline and daily during up to 8 chemotherapy cycles using supplemental questions on the Oral Mucositis Daily Questionnaire, a valid tool for collecting patient-reported outcomes of regimen-related mucosal injury. Patients scored CID severity from 0 “none” to 10 “worst possible,” and quantity from “little” to “severe” on a 5-point scale. Quality of life was measured using the FACT-G, and fatigue using the FACIT fatigue scale.

Results

CID occurred in 89 % of patients on FOLFIRI, 50 % on FOLFOX + monoclonal antibodies and 56 % on FOLFOX alone. The risk of a first episode was highest during Cycle 1 (35 %) and dropped to <10 % during Cycles 3–5. Patients with CID reported poorer quality of life scores than those without CID (77.1 vs 80.7).

Conclusions

Diarrhea occurs more commonly than typically appreciated during chemotherapy for CRC. Risk is highest during first exposure, suggesting variable susceptibility. Identification of this high-risk subgroup for prophylaxis could improve the quality of life.     

Evaluation of gefitinib efficacy according to body surface area in patients with non-small cell lung cancer harboring an EGFR mutation

Background

Exon 19 deletions and L858R point mutation are the most commonly encountered active epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC), and they predict greater efficacy of gefitinib therapy. The objective of this study was to evaluate whether body surface area (BSA) affects the efficacy of gefitinib in patients with NSCLC harboring an active EGFR mutation.

Methods

We reviewed the medical records of consecutive patients with advanced NSCLC harboring an active EGFR mutation who received gefitinib monotherapy. The median BSA value was used as the cutoff value to evaluate the impact of BSA on the efficacy of gefitinib.

Results

The median BSA of the 103 NSCLC patients harboring an active EGFR mutation was 1.45 m². The overall response rate, progression-free survival (PFS), and median survival time (MST) were 65.0 %, 11.3 months, and 26.2 months, respectively. There were no significant differences in clinical outcomes between the high-BSA group (BSA ≥ 1.45 m²) and low-BSA group (BSA < 1.45 m²), i.e., the response rates was 60.0 % and 69.8 %, respectively (P = 0.20), and their MST was 24.7 and 26.2 months, respectively (P = 0.78). Although BSA was predictive of PFS between high-BSA group and low-BSA group in the univariate analysis (9.0 and 12.2 months, P = 0.04), the multivariate analysis identified only performance status and smoking status as independent predictors of PFS.

Conclusions

The efficacy of gefitinib in patients with NSCLC harboring an EGFR mutation does not differ according to their BSA.     

The Application of Real-Time PCR Technique to Detect Rare Cell Clones with Primary T790M Substitution of EGFR Gene in Metastases of Non-small Cell Lung Cancer to Central Nervous System in Chemotherapy Naive Patients

The time-limited efficacy of reversible EGFR-TKIs in patients with advanced non-small cell lung cancer (NSCLC) with EGFR gene activating mutations is associated with development of treatment resistance after some period of therapy. This resistance predominantly results from secondary mutations located in EGFR gene, especially T790M substitution. There is limited information available concerning the prevalence of primary T790M mutations in patients with metastatic NSCLC tumors before treatment with EGFR-TKIs. The aim of work was to assess the prevalence of de novo T790M mutations in EGFR gene in tissue samples from NSCLC metastatases in central nervous system (CNS) in both chemotherapy and EGFR-TKI naive NSCLC patients. We analyzed DNA samples isolated from paraffin-embedded tissue from CNS metastases for T790M mutations using real-time PCR and TaqMan probe against the T790M mutant sequence. The tissue samples were taken during palliative neurosurgery in 143 NSCLC patients. Amplification of the T790M-specific sequence was detected in 25 patients (17.5 %). The quantity of mutated DNA was less than 1 % in all samples with amplification, and in vast majority (20 patients, 14 % of all samples) it was even less that 0.1 %. In 5 patients (3.5 %) quantity of mutated DNA ranged from 0.1 to 1 % and true positive results of T790M mutation presence in these patients were most possible. Amplification of this sequence was not concurrent with common EGFR mutations and was not associated with sex, smoking status and pathological type of cancer. There is a possibility to detect the primary T790M mutation in brain metastases of NSCLC in EGFR-TKIs naïve patients.     

Clinical significance of serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in patients with breast cancer

Insulin-like growth factor-1 (IGF-1) and its primary binding protein-3 (IGFBP-3) play an important role in cellular proliferation, differentiation and apoptosis in many tumors, including breast cancer (BC). The objective of this study was to determine the clinical significance of the serum levels of IGF-1 and IGFBP-3 in BC patients. A total of 96 patients with a pathologically confirmed diagnosis of BC were enrolled into this study. Serum IGF-1 and IGFBP-3 levels were determined by the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) methods. Age- and sex-matched 30 healthy controls were included in the analysis. The median age of diagnosis was 48 years (range: 29–80). Thirty-seven (39 %) consisted of metastatic disease. No significant difference in baseline serum was found in both IGF-1 and IGFBP-3 levels between BC patients and healthy controls (p?=?0.92 and p?=?0.26, respectively). None of the prognostic parameters analyzed was correlated significantly with the serum assay concentrations. Likewise, no correlations were also found between these serum concentrations and response to chemotherapy. No significant correlation was found between serum IGF-1 and IGFBP-3 levels in BC patients (r _s?=?0.048, p?=?0.66).The patients with elevated serum IGF-1 levels had favorable in survival than those with lower levels (p?=?0.05). However, serum IGFBP-3 concentrations were found no prognostic role for outcome (p?=?0.35). In conclusion, elevated serum IGF-1 level is afavorable prognostic factor for overall survival in BC patients.     

Impact of estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER2) co-expression on breast cancer disease characteristics: implications for tumor biology and research

ER and HER2 are critical drivers of breast cancer biology and can interact when co-expressed, but less data describe the impact of ER/HER2 co-expression on clinical disease characteristics. We studied the impact of ER and HER2 (co)-expression in a cohort of 1,187 patients with invasive breast cancer and compared disease characteristics among different groups according to ER and HER2 status. Age, tumor size, grade, nodal status, TNM stage, and metastatic sites were compared and significance determined using the appropriate t tests. All p values were two-tailed. Compared to ER-negative/HER2-negative disease as the control group, ER expression was associated with older age, smaller tumors, lower grade, earlier TNM stage, and increased bone involvement in de novo metastasis, while HER2 had no significant impact on these characteristics. ER and HER2 co-expression was associated with lower grade and higher bone involvement in de novo metastasis, reflecting a retained impact for ER. HER2 impact on ER-positive disease was reflected by younger age, higher grade and TNM stage, and increased frequency of visceral involvement in de novo metastasis. Within the ER-positive/HER2-positive group, triple positive breast cancer (ER+/PgR+/HER2+) was associated with younger age compared to ER+/PgR?/HER2+ disease (mean age of 50.8 vs. 56 years, p = 0.0226). PgR was also associated with younger age in ER+/HER2? disease with a mean age of 57.6 years in ER+/PgR+/HER2? disease vs. 63.4 years in ER+/PgR?/HER2? disease (p < 0.0001). In conclusion, ER has a profound impact on breast cancer characteristics, including a retained impact when co-expressed with HER2. Similarly, HER2 dramatically modulates ER-positive breast cancer making it more aggressive. PgR association with young age may be related to hormonal levels of the premenopausal state, with HER2 providing an earlier growth advantage in triple positive disease, suggesting a specific dependence for this subset on high estrogen levels.     

Prediction of thyroid extracapsular extension with cervical lymph node metastases (ECE-LN) by CEUS and BRAF expression in papillary thyroid carcinoma

The aim of our study was to find a specific imaging (contrast-enhanced ultrasound, CEUS) to detect extracapsular extension and cervical lymph node metastases (ECE-LNM) that associated with BRAF protein expression in papillary thyroid carcinoma (PTC). Preoperative utrasonography (US) or CEUS was performed in the diagnosis of extracapsular extension (ECE) in 317 patients with 369 PTC. BRAF protein status was tested on the primary tumor and lymph node involvement. The diagnostic accuracy of CEUS and US was evaluated after thyroid surgery. The association between CEUS and BRAF expression were then analyzed to investigate the diagnostic value of ECE-LNM in PTC. The sensitivity and specificity of CEUS were higher than those in US in the diagnosis of ECE in patients with PTC (91.1, 86.5 vs 49, 55 %). BRAF protein overexpression were significantly associated with ECE (P?=?0.0003) and lymph node metastasis (LNM) positive cases (P?=?0.0014). The results of CEUS, not US, have a significant correlation with BRAF expression status in PTC samples (P?BRAF protein expression status, the routine preoperative CEUS could have a good value in the diagnosis of ECE-LNM in PTC and facilitate a surgeon to improve further clinical management.     

Predictive value of APE1, BRCA1, ERCC1 and TUBB3 expression in patients with advanced non-small cell lung cancer (NSCLC) receiving first-line platinum–paclitaxel chemotherapy

Purpose

Drug resistance is not only one of the major obstacles to treatment but also a poor prognosis in advanced non-small cell lung cancer (NSCLC) patients. The aim of this study was to evaluate the predictive value of APE1, BRCA1, ERCC1 and TUBB3 in advanced NSCLC patients who received platinum–paclitaxel treatment.

Methods

One hundred and thirty-six advanced NSCLC patients, who were treated with first-line platinum–paclitaxel chemotherapy, were enrolled in this study. The protein expression levels of APE1, BRCA1, ERCC1 and TUBB3 were assessed by immunohistochemistry and analyzed for the association with response to chemotherapy and progression-free survival (PFS) and overall survival (OS).

Results

Patients with negative expression of APE1, ERCC1 or TUBB3 benefited from platinum plus paclitaxel regimen chemotherapy. ERCC1-negative patients had better PFS (P = 0.016) and OS (P = 0.030) compared with positive patients. Similarly, the APE1-negative patients showed better PFS (P = 0.004) and longer OS though statistically insignificant. Multivariate analysis showed that APE1 and ERCC1 were independent predictor for PFS (HR 2.07; P = 0.004 and HR 1.66; P = 0.016) and OS (HR 1.99; P = 0.008 and HR 1.64; P = 0.040). Moreover, patients with both APE1- and ERCC1-negative or both APE1- and TUBB3-negative tumors had significantly higher response rate, longer median PFS and OS following treatment with platinum and paclitaxel (P < 0.05).

Conclusion

The data indicate that APE1, ERCC1 and TUBB3 could be a useful biomarker to predict clinical outcome in patients with advanced NSCLC receiving first-line platinum–paclitaxel chemotherapy.     

Efficacy of S-1 plus cisplatin combination chemotherapy in patients with HER2-positive advanced gastric cancer

Background

Combination chemotherapy with trastuzumab and cisplatin plus capecitabine or 5-fluorouracil has been used as a standard regimen for HER2-positive gastric cancer (GC) since the Trastuzumab for Gastric Cancer (ToGA) trial. Before the ToGA trial, HER2-positive GC in Japan was treated with S-1 plus cisplatin (SP). The primary objective of this retrospective study was to explore the efficacy of SP in HER2-positive GC.

Methods

We reviewed patients who had received SP as first-line chemotherapy at our institute between April 2007 and March 2011 and from whom we had enough samples to examine HER2 status. Seventy-seven patients fulfilled the selection criteria and were tested for HER2 status with immunohistochemical staining (IHC) and fluorescence in situ hybridization. The patients’ backgrounds were investigated to evaluate the clinicopathologic features of their HER2-positive GC, including survival.

Results

Seven (9.1 %) of 77 patients were judged to be IHC3+, and all of these had predominantly differentiated histology. HER2 positivity was associated with differentiated histology (P = 0.016) and liver metastasis (P = 0.025). Median overall survival was 23.6 months [95 % confidence interval (CI) 0.8–44.7] in HER2-positive GC and 12.9 months (95 % CI 8.3–17.5) in HER2-negative disease, but the difference was not statistically significant (P = 0.615). In multivariate analysis, HER2 status was not associated with survival outcomes.

Conclusion

Because of the retrospective nature of this study, we cannot conclude whether HER2 status influences the survival of patients who receive SP as first-line chemotherapy. Our study provides important historical data for prospective phase II studies of SP plus trastuzumab.     

Relationships between VEGF protein expression and pathological characteristics of diffuse large B cell lymphoma: a meta-analysis

We carried out the current meta-analysis of relevant cohort studies in an attempt to investigate the relationships between vascular endothelial growth factor (VEGF) expression and pathological characteristics of diffuse large B cell lymphoma (DLBCL). The following electronic databases were searched for relevant articles without any language restrictions: Web of Science (1945?~?2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966?~?2013), EMBASE (1980?~?2013), CINAHL (1982?~?2013), and the Chinese Biomedical Database (CBM) (1982?~?2013). Meta-analyses were conducted with the use of STATA software (version 12.0, Stata Corporation, College Station, TX, USA). Odds ratios (ORs) and its 95 % confidence interval (95 % CI) were calculated. Nine clinical cohort studies with a total of 789 DLBCL patients met our inclusion criteria. The meta-analysis results showed that patients with positive VEGF expression had higher international prognostic index (IPI) scores than VEGF-negative patients (OR?=?5.12, 95 % CI?=?2.70?~?9.71, P?VEGF expression and evaluated lactate dehydrogenase (LDH) levels (OR?=?2.50, 95 % CI?=?1.36?~?4.60, P?=?0.003). We also found that patients with positive B symptoms had increased level of VEGF expression (OR?=?2.02, 95 % CI?=?1.08?~?3.77, P?=?0.027). The findings of our meta-analysis provide reliable evidence that VEGF expression may be strongly correlated with pathological characteristics of DLBCL.     

Comparison of ERCP,EUS, and ERCP combined with EUS in diagnosing pancreatic neoplasms: a systematic review and meta-analysis

In the current study, we performed a systematic review of literature pertaining to the diagnostic value of endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasonography (EUS), and combined ERCP plus EUS to pancreatic cancer. We searched MEDLINE, OVID, and the Cochrane Library for studies evaluating diagnostic validity of ERCP, EUS, and ERCP plus EUS between January 1989 and May 2014. We obtained pooled estimates of sensitivity, specificity, and summary receiver operating characteristic curves (SROC). A total of 10 studies that included 669 patients who fulfilled all of the inclusion criteria were considered for inclusion in the analysis. The pooled sensitivities of EUS, ERCP, and EUS plus ERCP were 76.7, 57.9, and 79.9 %, respectively. The pooled specificities were 91.7, 90.6, and 94.2 %, respectively. The *Q index estimates were 0.828, 0.862, and 0.896, respectively. The *Q indices for EUS and EUS plus ERCP were significantly higher compared with ERCP (P?=?0.010 and 0.008, respectively). Our meta-analysis showed that ERCP plus EUS was associated with a high diagnostic value for the detection of pancreatic neoplasms compared with ERCP and EUS alone.     

Relationship between chemotherapy and prognosis in different subtypes of node-negative breast cancer

Knowledge is limited about the relationship between chemotherapy and prognosis among the subtypes of axillary node-negative breast cancer (ANNBC). In this study, a population including 2,236 primary and operable ANNBC patients, with a median age of 53, were included. All breast tumors were classified into five immunohistochemically defined subtypes—luminal A, luminal B, luminal human epidermal growth factor receptor 2 (HER2), HER2 overexpression, and triple negative. With a median follow-up of 73.6 months, the rate of relapse was lowest in luminal A (6.5 %) and highest in HER2 overexpression subtype (16.4 %). Multivariate analysis indicated that the risks of relapse and death were enhanced in HER2 overexpression and triple-negative (TN) subtypes, and these two subtypes were independent predictors of relapse and death. Luminal A patients with risk factors could benefit from chemotherapy in terms of relapse-free survival (RFS). The relapse rate of TN patients after chemotherapy with taxanes was lower compared with that after chemotherapy without taxanes. In conclusion, women with ANNBC were at higher risks of relapse and death if suffering from HER2 overexpression or TN diseases. Chemotherapy could reduce the recurrence rate of luminal A patients with risk factors. TN patients may benefit from adjuvant chemotherapy containing taxanes.     

Expression of MLH1 and MSH2 in urothelial carcinoma of the renal pelvis

In this study, we investigated microsatellite instability in urothelial carcinoma of the renal pelvis by lack of immunohistochemical staining for MLH1 and MSH2. The study included 44 cases of urothelial carcinoma of the renal pelvis obtained from radical nephroureterectomy specimens at our institution. We evaluated the loss of nuclear immunohistochemical staining of MLH1 and MSH2. Eight of 44 (18 %) patients had negative MLH1 expression and 25/44 (57 %) patients had negative MSH2 expression. Six of 8 (75 %) patients with negative MLH1 expression were male and 2/8 (25 %) patients were female. Nineteen of 25 (75 %) patients with negative MSH2 expression were male, and 6/25 (24 %) patients were female. Seven of 8 (88 %) cases with negative MLH1 expression were high-grade urothelial carcinoma, and 21/25 (84 %) cases with negative MSH2 expression were high-grade urothelial carcinoma. Twenty-one of 44 (48 %) cases had an inverted growth pattern, of which 3/21 (14 %) cases had negative MLH1 expression and 14/21 (67 %) cases had negative MSH2 expression. Our study showed that microsatellite instability based on negative expression of MLH1 and MSH2 was more common in male patients with high-grade urothelial carcinoma. There is a strong correlation between inverted growth pattern and negative MSH2 expression. Microsatellite instability testing should be performed in patients with upper urinary tract carcinoma and may have prognostic value.     

Decreasing relapse in colorectal cancer patients treated with cetuximab by using the activating KRAS detection chip

The KRAS oncogene was among the first genetic alterations in colorectal cancer (CRC) to be discovered. Moreover, KRAS somatic mutations might be used for predicting the efficiency of anti-epidermal growth factor receptor therapeutic drugs. Because the KRAS mutations are similar in the primary CRC and/or the CRC metastasis, KRAS mutation testing can be performed on both specimen types. The purpose of this study was to investigate the clinical advantage of using a KRAS pathway-associated molecule analysis chip to analyze CRC patients treated with cetuximab. Our laboratory developed a KRAS pathway-associated molecule analysis chip and a weighted enzymatic chip array (WEnCA) technique, activating KRAS detection chip, which can detect KRAS mutation status by screening circulating cancer cells in the bloodstream. We prospectively enrolled 210 stage II–III CRC patients who received adjuvant oxaliplatin plus infusional 5-fluorouracil/leucovorin (FOLFOX)-4 chemotherapy with or without cetuximab. We compared the chip results of preoperative blood specimens with disease control status in these patients. Among the 168 CRC patients with negative chip results, 119 were treated with FOLFOX-4 plus cetuximab chemotherapy, and their relapse rate was 35.3 % (42/119). In contrast, the relapse rate was 71.4 % among the patients with negative chip results who received FOLFOX-4 treatment alone (35/49). Negative chip results were significantly correlated with better treatment outcomes in the FOLFOX-4 plus cetuximab group (P?KRAS detection chip is a potential tool for predicting clinical outcomes in CRC patients following FOLFOX-4 treatment with or without cetuximab therapy.     

A comparative analysis of EGFR mutation status in association with the efficacy of TKI in combination with WBRT/SRS/surgery plus chemotherapy in brain metastasis from non-small cell lung cancer

We proposed to identify the efficacy of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) using whole brain radiotherapy (WBRT)/stereotactic radiosurgery (SRS)/surgery in brain metastases from patients with non-small cell lung cancer (NSCLC) and clarify the association between treatment outcome and EGFR gene mutation status. A total of 282 patients with NSCLC brain metastases who underwent WBRT/SRS/surgery alone or in combination with TKI were enrolled in our study from 2003–2013. Amplification mutation refractory system technology was used to determine the EGFR mutation status in 109 tissue samples. EGFR mutation detection was performed in 109 patients with tumor tissues. The EGFR positive rate was 50 % (55/109), including 26 exon 19 deletions and 24 L858R mutations. The median follow-up time was 28 months. The median overall survival, median progression-free survival of intracranial disease, and median progression-free survival of extracranial disease was significantly longer for patients with TKI treatment (31.9 vs 17.0 months, P < 0.0001; 19.8 vs 12.0 months, P < 0.0001; and 19.6 vs 12.3 months, P < 0.0001; respectively). In subgroup analysis within the TKI group, patients harboring EGFR mutations had better extracranial disease control (20.4 vs 14.1 months, P = 0.032). Administration of TKI agents with conventional therapy compared with conventional therapy alone might be beneficial for overall survival, progression-free survival of intracranial disease and progression-free survival of extracranial disease in patients with brain metastases from NSCLC independent of EGFR mutations.     

Development of Serous Ovarian Cancer is Associated with the Expression of Homologous Recombination Pathway Proteins

To investigate the expressions of key markers in the homologous recombination (HR) pathway and the correlation with clinicopathological parameters in serous ovarian cancer (SOC). We analyzed the protein expression of MRE11, MDC1, ATM, ATR and BRCA1 by immunohistochemistry (IHC) in 97 SOC samples, and correlated with clinical parameters including age, tumor grades, clinical stage, status of menstruation and chemotherapy. Low expression of MRE11 and MDC1 was detected in 14.4 % and 3.1 % of the patient samples, and negative expression of ATM, ATR and BRCA1 was found in 11.3 %, 6.3 % and 29.9 % of the patient samples, respectively. ATR deficiency was significantly associated with menopause (P?=?0.025), strong expression of ATM (P?=?0.017) and MRE11 (P?=?0.040) with pre-menopausal SOC, strong expression of MRE11 (P?=?0.016) with low tumor grade, and strong expression of BRCA1 (P?=?0.015) with early clinical stage. In addition, low expression of MRE11 was strongly associated with negativity of ATR (P?BRCA1 (P?=?0.004) Furthermore, ATR deficiency was associated with low expression of ATM (P?=?0.028) and loss expression of BRCA1 (P?=?0.009). Our results suggest that reduced expression or loss of proteins in HR pathway is associated with SOC development. Abnormality of MRE11 and BRCA1 are strongly associated with late clinical stage in SOC patients.