Predictive Factors For Distant Metastasis Research Articles

Overexpression of the NEK9–EG5 axis is a novel metastatic marker in pathologic stage T3 colon cancer

NEK9 is a key player in the NEK9–EG5 axis for microtubule polymerization, chromosome alignment, and mitosis. In present study, we investigated the altered expression of the NEK9, EG5 and acetyl-α-tubulin as well as common epithelial–mesenchymal transition (EMT) markers (E-cadherin, vimentin, claudin-1, and β-catenin) through the immunohistochemistry analysis of 138 patients with pathologic T3 (pT3) stage colon cancers, and evaluated their metastatic potential. NEK9 expression showed an association with distant metastasis (P = 0.032) and was an independent predictive factor for distant metastasis (HR = 3.365, P < 0.001) by multivariate analysis, which was more significant than either the regional nodal metastasis (HR = 2.496, P = 0.007) or lymphovascular invasion (HR = 2.090, P = 0.153). Positive correlations were observed between NEK9 and EG5 or acetyl-α-tubulin (r = 0.236 and P = 0.007; r = 0.181 and P = 0.038, respectively) and concordant overexpression of the NEK9–EG5 axis was further confirmed in colon cancer cell lines. These findings collectively suggest that the overexpression of the NEK9–EG5 axis is present and associated with distant metastasis in colon cancer. These biomarkers might be useful for predicting metastatic potential among the patients with pT3 colon cancers.

An Elusive Case of Pleural Effusion

The incidence of distant metastasis in head and neck Squamous Cell Carcinoma (SCC) is relatively low. The most frequently involved sites for distant metastasis are lungs, followed by bone and liver. The most important predictive factors for distant metastasis appear to be site of the primary tumour (hypopharynx), advanced T- and N-classification, locoregional control and histologic grade. A 61- year-old male, chronic smoker, presented with complaints of grade 4 mMRC (Modified Medical Research Council) dyspnoea. He had left-sided buccal mucosal SCC (locally advanced) and was on palliative chemotherapy. He had undergone treatment for pulmonary tuberculosis seven years back. He was tachypneic and clinical examination revealed absent breath sounds in the left hemithorax. Chest radiograph showed a massive left pleural effusion which was found to be exudative after therapeutic thoracocentesis. Cytology tests were negative for malignant cells. Positron Emission Tomography (PET) scan showed uptake along the left pleura (SUV Max-5.06) and left buccal mucosa (SUV Max -4.1). Thoracoscopic frozen section pleural biopsy revealed metastatic squamous cell carcinomatous deposits in the pleura. On table pleurodesis was done with doxycycline. The patient was continued on palliation with no recurrent effusion. However, he succumbed to the disease after eight months. This case report describes a rare case of malignant pleural effusion from a primary buccal mucosal SCC without any concurrent lung involvement.

Constructing and validating nomograms to predict risk and prognostic factors of distant metastasis in urothelial bladder cancer patients: a population-based retrospective study

BackgroundUrothelial carcinoma is the most common type of bladder cancer worldwide and it has a poor prognosis for patients with distant metastasis. Nomograms are frequently used in clinical research, but no research has evaluated the diagnostic and prognostic factors of distant metastasis in urothelial bladder cancer (UBC).MethodsThe Surveillance, Epidemiology, and End Results database was used to analyze all patients diagnosed with UBC between 2000 and 2017. Lasso regression was used to identify the potential risk predictive factors for distant metastasis in UBC. Univariate and multivariate Cox proportional hazard regression analyses were performed to determine independent prognostic factors for distant metastasis urothelial bladder cancer (DMUBC). Subsequently, two nomograms were constructed based on the above models. The receiver operating characteristic (ROC), and calibration curves were performed to evaluate the two nomograms.ResultsThe study included 73,264 patients with UBC, with 2,129 (2.9%) having distant metastasis at the time of diagnosis. In the diagnostic model, tumor size, histologic type, and stage N and T were all important risk predictive factors for distant metastasis of UBC. In the prognostic model, age, tumor size, surgery, and chemotherapy were independent factors affecting the prognosis of DMUBC. DCA, ROC, calibration, and Kaplan–Meier (K–M) survival curves reveal that the two nomograms can effectively predict the diagnosis and prognosis of DMUBC.ConclusionThe developed nomograms are practical methods for predicting the occurrence risk and prognosis of distant metastasis urothelial bladder cancer patients, which may benefit the clinical decision-making process.

Clinico-pathologic factors associated with the occurrence of early and late metastatic spread in a cohort of breast cancer patients.

Distant metastatic spread in breast cancer patients is a complex phenomenon involving several prognostic factors. We focused our analysis on early metastatic breast cancer (EMBC) (occurring during the first 36 months) versus late metastatic breast cancer (LMBC) (occurring beyond 3 years) in order to ascertain their possible differential predictive factors. diagnostic, surgical, and follow-up data were assessed for consecutive patients with breast cancer undergoing surgery between 1997 and 2019. We analysed the predictive factors for distant metastasis using both univariate and multivariate analysis. The median follow-up for this cohort of 2708 patients was 89 months. The median metastasis-free interval (FMI) for metastasis patients was 38 months (17 months for EMBC group and 76 months for LMBC group). Distant metastases developed in 12.9% (350/2708); 48% (168/350) of them as EMBC and 52% (182/350) as LMBC. Loco-regional recurrence and nodal extracapsular extension were the only common predictors for both. EMBC and LMBC appeared as two separate conditions, with a different outcome. In the EMBC group, tumour proliferation related factors were significant (histological grade, tumour size, body mass index), whereas for LMBC, other slow-acting factors seemed to be involved (screening program, tumour burden, bilateral tumour).

Elevated preradiotherapy serum lactate dehydrogenase predicts distant metastasis for lymphoepithelial carcinoma of major salivary gland following postoperative radiotherapy.

To evaluate the predicting factors associated with distant metastasis (DM) for lymphoepithelial carcinoma of salivary gland (LECSG) following postoperative radiotherapy (PORT). We retrospectively collected 160 eligible patients from two cancer institutions. The DM rate was evaluated using competing risk method. The median follow-up time was 65.6 months. Elevated preradiotherapy serum LDH (ratio >0.5) (p=0.006) and N classification (N2-3) (p=0.001) were independently associated with DM for the LECSG. After the risk stratification, the high-risk subgroup was defined as the patients presented higher risk score (score >0), whereas 5-year cumulative incidence of DM in the high- and low-risk group was 30.9% and 6.0%, respectively (p < 0.001). Moreover, a significantly worse overall survival (OS) was observed in the high-risk patients compared with the low-risk subgroup (5-year OS: 83.9% vs. 97.8%, p=0.006). Elevated preradiotherapy serum LDH could serve as a predictive factor for DM in the LECSG following PORT.

Abstract P3-03-06: Internal mammary chain sentinel nodes in early stage breast cancer patients: Towards selective removal

Abstract Background Internal mammary chain (IMC) sentinel nodes (SN) are visible in 1 out of 5 breast cancer patients on lymph scintigraphy after intra- or peritumoral injection of a radiopharmaceutical. The IMC SN status affects prognosis and treatment of breast cancer and IMC radiotherapy improves survival in selected patients. In contrast to the axillary SN, removal of the IMC SN is not routinely performed and often technically challenging. This study aims at determining the effect of IMC SN biopsy on recurrence-free survival (RFS) and overall survival (OS) and the identification of predictive factors for the development of IMC- and distant metastases. Methods All patients with IMC SNs were selected from a prospective database from 1999 to 2007. Following intratumoral injection of technetium-99m, conventional lymphoscintigraphy was performed. Sentinel nodes were removed in all regions with lymphatic drainage on scintigraphy. The RFS and OS were calculated for the total group and subgroups with tumor-positive, tumor-negative or non-removed IMC SN. Predictive factors were identified for tumor-positive IMC SN and for distant metastasis by regression analysis. Results Internal mammary chain SN biopsy was performed in 287 out of 336 patients (85%). The IMC SN was tumor-positive in 38 patients (13%). Patients with IMC metastasis had poorer OS compared to patients without IMC metastasis or a non-removed IMC SN (57%, 82% and 59% 10- year OS, respectively, p = 0.002). These patients also had worse RFS, mainly due to by the development of distant metastases (68%, 84% and 61% RFS, respectively, p = 0.002). Multivariable predictive for tumor-positive IMC SN were axillary metastases (PPV = 38.5%). Predictive factors for distant metastasis were tumor-positive IMC SN (HR 2.5, 95% CI; 1.0 - 5.8, p = 0.04), not removed IMC SN (HR 2.3, 95% CI; 1.0 - 5.1, P = 0.05), tumor diameter &amp;gt;1.5cm (HR 3.5, 95% CI; 1.6 - 8.4, p &amp;lt; 0.00) and age &amp;gt;65 years (HR 3.1, 95% CI; 1.2 - 7.7, p = 0.02, reference &amp;lt;50 years). Conclusion Breast cancer patients with tumor-positive IMC SN have worse 10- year survival than patients with tumor-negative IMC SN, mainly due to the development of distant metastasis. The clinically relevant predictive factor for distant metastasis is tumor size &amp;gt;1.5cm. Radiotherapy of the IMC can improve survival. However, the cardiotoxicity of parasternal radiotherapy must be weighed against the expected survival benefit. Therefore, our current protocol is to perform IMC SN biopsy in patients younger than 70 years with a tumor diameter &amp;gt;1.5cm. Citation Format: van Loevezijn AA, Bartels SA, van Duijnhoven FH, Heemsbergen WD, Bosma SC, Elkhuizen PH, Donswijk ML, Rutgers EJ, Oldenburg HS, Vrancken Peeters M-JT, van der Ploeg IM. Internal mammary chain sentinel nodes in early stage breast cancer patients: Towards selective removal [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-06.

Pre-treatment CD8+ tumour-infiltrating lymphocyte density predicts distant metastasis after definitive treatment in patients with stage III/IV hypopharyngeal squamous cell carcinoma.

Although inflammatory markers, such as the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and local immune markers have been shown to have prognostic utility, limited information is available regarding inflammatory and pre-existing tumour-infiltrating lymphocyte density and their association with prognosis in patients with hypopharyngeal squamous cell carcinoma. We investigated the prognostic ability of inflammatory markers and tumour-infiltrating lymphocyte density in stage III and stage IV hypopharyngeal squamous cell carcinoma patients receiving definitive treatment. Retrospective cohort study. Kurume University Hospital. Ninety-six stage III or stage IV hypopharyngeal squamous cell carcinoma patients treated at the Kurume University Hospital between 2000 and 2014. Inflammatory markers and pre-treatment tumour-infiltrating lymphocyte density were examined from recorded haematologic data and immunohistochemical analysis. Multivariate analyses showed that the CD8+ tumour-infiltrating lymphocyte density was an independent predictive factor for distant metastasis and overall survival, whereas inflammatory markers, including the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, were not correlated with distant metastasis or overall survival. Higher pre-treatment CD8+ tumour-infiltrating lymphocyte density is a useful predictive biomarker for reduced distant metastasis and better prognosis.

Tumor location is an independent predictive factor for distant metastasis and metastatic sites of rectal adenocarcinoma in patients receiving total mesorectal excision.

Background and Objectives: To evaluate the predictive factor for and patterns of distant metastasis in patients with rectal adenocarcinoma receiving total mesorectal excision (TME).Methods: We enrolled 217 consecutive patients who had histologically confirmed rectal adenocarcinoma and underwent surgery at Taipei Medical University- Wanfang Hospital between January 2000 and December 2014. TME was performed in all patients undergoing a sphincter-sparing procedure or abdominal perineal resection of rectal cancer. We performed univariate and multivariate Cox regression analyses of the distant metastasis rate in all patients to evaluate predictive factors. Overall survival (OS) rates were calculated using the Kaplan-Meier method, and Kaplan-Meier survival curves were compared using the log-rank test.Results: A multivariate Cox regression analysis of the distant metastasis rate in patients with rectal adenocarcinoma identified tumor locations and American Joint Committee on Cancer (AJCC) stages as prognostic risk factors. The adjusted hazard ratios (aHRs) of distant metastasis for the upper-third, middle-third, and AJCC stage I-II cancers were 0.08 (95% CI, 0.01-0.69; p = 0.021), 0.41 (95% CI, 0.15-0.99; p = 0.047), and 0.20 (95% CI, 0.10-0.66; p = 0.008), respectively. The 5-year lung metastasis rates among patients with upper-, middle-, and lower-third rectal cancers were 0%, 3.37%, and 13.33%, respectively (log-rank, p = 0.001), and the 5-year liver metastasis rates among patients with upper-, middle-, and lower-third rectal cancers were 2.12%, 9.10%, and 11.76%, respectively (log-rank, p = 0.096). The 5-year OS rates also differed with different rectal adenocarcinoma locations. The 5-year OS rates for upper, middle, and lower rectal cancers were 96%, 86%, and 64%, respectively (log-rank, p < 0.001).Conclusion: A poor OS rate and high lung or liver metastasis rate were observed in distal rectal adenocarcinoma. Longer intensive surveillance of the chest, abdomen, and pelvis after TME in distal rectal adenocarcinoma could be necessary.

Predictive and prognostic factors for patients with locoregionally advanced laryngeal carcinoma treated with surgical multimodality protocol.

The prognosis is suboptimal in patients with locoregionally advanced laryngeal carcinoma even after multimodality protocols. The purpose of this study was to determine the potential influential factors that have an impact on the development of locoregional recurrence, distant metastasis, and oncological outcomes in patients with locoregionally advanced laryngeal carcinoma who had surgical multimodality protocols. A sample size of 85 cases was determined based on a power of 90% and an effect size of α 2=0.05. A retrospective analysis of 357 patients with a diagnosis of laryngeal cancer between 2002 and 2015 was performed. Eighteen variables based on sociodemographic, clinical, histopathological and treatment data were analyzed. Medical records of 85 consecutive patients with locoregionally advanced laryngeal carcinoma who underwent surgical multimodality protocols were reviewed. Five-year overall, disease-specific, disease-free, locoregional recurrence-free and distant metastasis-free survival were 68.7, 78.0, 69.6, 68.9 and 69.2%, respectively. Extracapsular extension was an independent predictive factor for locoregional recurrence. Pathologic tumor volume was an independent predictive factor for distant metastasis. pT-stage was an independent prognostic factor for 5-year overall survival, disease-free survival, locoregional recurrence-free survival and distant metastasis-free survival. High volume, pT4a laryngeal tumors with extracapsular extension are associated with a high risk of locoregional recurrence and distant metastasis; and have poor oncological outcomes in patients with locoregionally advanced laryngeal carcinoma treated with surgical multimodality protocols.

Predictors of Distant Metastasis after Radical Surgery Followed by Postoperative Radiotherapy with or without Chemotherapy for Oropharyngeal Cancer.

PurposeWe investigated the prognostic factors for distant metastasis (DM) in patients with locally advanced oropharyngeal cancer (OPC) treated with surgery and adjuvant radiotherapy with or without concurrent chemotherapy.Materials and MethodsEighty-five patients treated between January 1995 and August 2014 were evaluated retrospectively. Data regarding the pathological tumour and nodal status, human papillomavirus (HPV) status, treatment characteristics, and pretreatment maximum standardized uptake value (SUVmax) of 18-fluoro-2-deoxyglucose positron emission tomography–computed tomography scan (18F-FDG PET-CT) were evaluated, and their influence on DM and survival outcomes were analyzed.ResultsMedian follow-up period was 48.0 months. Recurrence was observed in 20 patients, including locoregional recurrence and DM. DM was observed in 13 patients. A multivariate analysis confirmed that the presence of lymphovascular invasion (p=0.031), lower neck lymph node (LN) involvement (p=0.006), SUVmax ≥ 9.7 (p=0.014), and tumour size ≥ 3 cm (p=0.037) significantly affected DM. HPV status was not associated with DM. Perineural invasion (p=0.048), lower neck LNinvolvement (p=0.008), SUVmax ≥ 9.7 (p=0.019), and tumour size ≥ 3 cm (p=0.033) were also significant factors for the DM-free survival rate.ConclusionLower neck LN involvement, high SUVmax in pretreatment 18F-FDG PET-CT, and large tumour size were predictive factors for DM in patients of OPC.

Identification of a predictive factor for distant metastasis in esophageal squamous cell carcinoma after definitive chemoradiotherapy

Distant metastasis (DM) after definitive chemoradiotherapy has not been a focus of research in esophageal carcinoma. At present, local-regional control is improving following advances in salvage treatments after definitive chemoradiotherapy. There is a need to focus on suppressing the development of DM. The aim of this study was to identify pre-treatment factors associated with DM after definitive chemoradiotherapy. This study included 144 patients with thoracic esophageal squamous cell carcinoma (Stage I/II/III/IV; 35/17/69/23) (TNM 7th) who underwent definitive chemoradiotherapy; >50Gy was prescribed to all gross tumors with concurrent administration of 5-fluorouracil±platinum. Pre-treatment factors included age, gender, performance status, tumor location, T/N/M status, tumor length, size of metastatic lymph nodes (LN size), and the presence of intramural metastasis or multiple primary tumors. The effects of pre-treatment factors on overall survival (OS) and DM were evaluated. The median follow-up period was 48months. DM occurred as an initial progression in 21% of patients, and LN size correlated with DM development (hazard ratio [HR]=5.12; p=0.0013) and poor OS (HR=2.20; p=0.0076) in univariate and multivariate analyses. LN size is a quantitative pre-treatment prognostic factor that should be assessed prior to definitive chemoradiotherapy. Patients with large metastatic lymph nodes are at high risk of DM and should be monitored.

Expression levels of SOX2, KLF4 and brachyury transcription factors are associated with metastasis and poor prognosis in oral squamous cell carcinoma.

The prognosis of oral squamous cell carcinoma (OSCC) patients is affected by tumor recurrence and metastasis, and cancer stem cells are hypothesized to be involved in these processes. Thus, the aim of the present study was to determine whether the expression levels of five stem cell-related transcription factors, sex determining region Y-box 2 (SOX2), octamer-binding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (c-Myc), Krüppel-like factor 4 (KLF4) and brachyury, are associated with metastasis and survival in OSCC. Immunohistochemistry was performed to analyze the expression of these proteins in biopsy specimens obtained from 108 OSCC patients. The results revealed that the expression of SOX2, Oct4, KLF4 and brachyury were significantly associated with lymph node metastasis (P=0.002, P=0.031, P=0.003 and P=0.007, respectively). In addition, the expression of KLF4 and brachyury were significantly associated with distant metastasis (P=0.014 and P=0.012, respectively). Furthermore, multivariate analysis revealed that SOX2 and KLF4 are predictive factors for lymph node metastasis [odds ratios (ORs), 4.526 and 4.851, respectively], and KLF4 is also a predictive factor for distant metastasis (OR, 9.607). In addition, OSCC patients with low co-expression of SOX2, KLF4 and brachyury exhibited a significantly lower disease-specific survival rate (78.6 vs. 100%; P=0.025; χ2=5.033) and disease-free survival rate (60.7 vs. 90.9%; P=0.015; χ2=5.897) when compared with OSCC patients with high co-expression of these factors. The results indicate that SOX2, KLF4 and brachyury serve important roles in tumor progression, and these transcription factors may thus represent clinically useful prognostic markers for OSCC.

Outcomes and prognostic factors of distant metastasis in patients with advanced cervical squamous cell carcinoma treated with concurrent chemoradiotherapy

To evaluate the outcomes and prognostic factors of distant metastasis in patients with advanced cervical squamous cell carcinoma treated with concurrent chemoradiotherapy (CCRT). A total of 118 patients with International Federation of Gynecology and Obstetrics (FIGO, 2009 version) stage II b-IVa cervical squamous cell carcinoma treated with CCRT between 2006 and 2010 in the Second Affiliated Hospital of Dalian Medical University were analyzed. Their median age was 48 years (range, 23-70 years). FIGO stages were as follows: IIb stage 56 cases, IIIa stage 6 cases, IIIb stage 52 cases, and IVa stage 4 cases. Of the all patients, 55 cases showed bulkly tumor (tumor size >4 cm) and 35 cases were pelvic lymph node positive. Forty patients had pretreatment hemoglobin (Hb) levels no greater than 110 g/L. Patients with elevated squamous cell carcinoma antigen (SCC- Ag) >1.5 µg/L before CCRT and at one month after CCRT were 91 cases and 34 cases, respectively. Kaplan-Meier method was used to estimate survival. For the analysis of prognostic factors affecting distant metastasis, log- rank test was used for univariate analysis, and Cox proportional hazard model was used for multivariate analysis. Thirty- seven patients were diagnosed with recurrence, 19 cases of whom developed distant metastasis, 13 cases developed loco-regional recurrence and 5 cases had both distant and loco-regional recurrence. The 5- year overall survival rates and distant disease- free survival of all patients were 64.0% and 78.8% , respectively. Two patients had grade 3 acute gastrointestinal toxicity (mainly diarrhea) and 20 cases had grade 3 to 4 hematologic toxicity. Seven patients experienced grade 3 to 4 late toxicity, 5 cases of them were gastrointestinal and 2 cases were genitourinary toxicity. Univariate analysis showed that FIGO stages, SCC-Ag level at one month after treatment, pretreatment hemoglobin level, and pelvic lymph node metastasis were significantly correlated with distant metastasis (all P < 0.05). Multivariate analysis showed that FIGO stage, SCC- Ag level at one month after treatment, and pelvic lymph node metastasis were independent prognostic factors for distant metastasis (all P < 0.05). For stage IIb-IVa cervical squamous cell carcinoma, the regimen of CCRT was efficacious and safe. The predictive factors for distant metastasis in patients with IIb-IVa stage squamous cell carcinoma of cervix treated with CCRT included FIGO stage, SCC- Ag level at one month after treatment, and pelvic lymph node metastasis. New treatment strategies should be considered to control distant metastasis for these patients.

Risk Factors and Prognosis for Myoepithelial Carcinoma of the Major Salivary Glands.

The clinical behavior and treatment outcomes of salivary gland myoepithelial carcinoma have yet to be clearly defined. The current study investigated risk factors and prognoses for this tumor. A retrospective review of the medical records for 32 patients with myoepithelial carcinoma of the major salivary glands was performed. Their clinical parameters were assessed to identify correlations with local-regional recurrence, distant metastasis, and survival. The 5-year survival rate was 71 %. Of the reviewed patients, 41 % had local-regional recurrences, and 22 % had distant metastases. Age of 60 years or younger was a predictive factor for distant metastasis. Patients with neck lymph nodes clinically positive for carcinoma had shorter overall survival durations than those with nodes negative for carcinoma. Myoepithelial carcinoma of the major salivary glands is characterized by a high incidence of local-regional recurrence and distant metastasis. Adjuvant therapy is indicated for selected patients with high-risk disease.

Adding maximum standard uptake value of primary lesion and lymph nodes in 18F-fluorodeoxyglucose PET helps predict distant metastasis in patients with nasopharyngeal carcinoma.

ObjectiveTo find out the most valuable parameter of 18F-Fluorodeoxyglucose positron emission tomography for predicting distant metastasis in nasopharyngeal carcinoma.MethodsFrom June 2007 through December 2010, 43 non-metastatic NPC patients who underwent 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) before radical Intensity-Modulated Radiation Therapy were enrolled and reviewed retrospectively. PET parameters including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glucose (TLG) of both primary tumor and cervical lymph nodes were calculated. Total SUVmax were recorded as the sum of SUVmax of primary tumor and cervical lymph nodes. Total SUVmean, Total MTV and Total TLG were calculated in the same way as Total SUVmax.ResultsThe median follow-up was 32 months (range, 23–68 months). Distant metastasis was the main pattern of treatment failure. Univariate analysis showed higher SUVmax, SUVmean, MTV, and TLG of primary tumor, Total SUVmax, Total MTV, Total TLG, and stage T3-4 were factors predicting for significantly poorer distant metastasis-free survival (p = 0.042, p = 0.008, p = 0.023, p = 0.023, p = 0.024, p = 0.033, p = 0.016, p = 0.015). In multivariate analysis, Total SUVmax was the independent predictive factor for distant metastasis (p = 0.046). Spearman Rank correlation analysis showed mediate to strong correlationship between Total SUVmax and SUVmax-T, and between Total SUVmax and SUVmax-N(Spearman coefficient:0.568 and 0.834;p = 0.000 and p = 0.000).ConclusionsPreliminary results indicated that Total SUVmax was an independently predictive factor for distant metastasis in patients of nasopharyngeal carcinoma treated with Intensity-Modulated Radiation Therapy.

Occult Lymph Node Metastases Increase Locoregional Recurrence in Differentiated Thyroid Carcinoma

The impact of occult lymph node metastasis (OLNM) on locoregional recurrence (LRR) and survival in patients with NO differentiated thyroid carcinoma is unclear, because no large study has been carried out. A retrospective study was conducted in our department to assess the influence of OLNM. We included 201 patients treated by prophylactic neck dissection for NO differentiated thyroid carcinoma between 1974 and 2006. The incidence of OLNM and predictive factors for recurrence and survival were assessed. The incidence of OLNM was 20%. Necks were involved at levels VI, III, II, IV, V, and I, in decreasing order of frequency. After a mean follow-up of 9 years, the rate of LRR was 8.9% and the rate of distant metastasis was 3.4%. An age of greater than 55 years and the presence of OLNM were predictive factors for LRR. An age of greater than 55 years and the presence of LRR were predictive factors for distant metastasis. The presence of distant metastasis was the only factor that significantly and independently influenced the disease-specific survival. We found that OLNM occurred in only 20% of NO patients. The presence and especially the number of OLNMs on neck dissection were major risk factors for LRR in this study, but did not affect the disease-specific survival.

ECA39 is a novel distant metastasis-related biomarker in colorectal cancer.

To investigate the possible role of polysaccharide-K (PSK) -related markers in predicting distant metastasis and in the clinical outcome of colorectal cancer (CRC). Firstly, we used protein microarrays to analyze the in vitro expression profiles of potential PSK-related markers in the human colorectal adenocarcinoma cell line SW480, which carries a mutant p53 gene. Then, we investigated the clinical implications of these markers in the prognosis of CRC patients. ECA39, a direct target of c-Myc, was identified as a candidate protein affected by the anti-metastatic effects of PSK. Immunohistochemistry revealed that ECA39 was expressed at significantly higher levels in tumor tissues with distant metastases compared to those without (P<0.00001). Positive ECA39 expression was shown to be highly reliable for the prediction of distant metastases (sensitivity: 86.7%, specificity: 90%, positive predictive value: 86.7%, negative predictive value: 90%). A significantly higher cumulative 5-yr disease free survival rate was observed in the ECA39-negative patient group (77.3%) compared with the ECA39-positive patient group (25.8%) (P<0.05). Our results suggest that ECA39 is a dominant predictive factor for distant metastasis in patients with advanced CRC and that its suppression by PSK might represent a useful application of immunotherapy as part of a program of integrated medicine.

Predictive factors for distant metastasis from oral and oropharyngeal squamous cell carcinoma

The presence of distant metastasis after the initial treatment of head and neck squamous cell carcinoma is not considered a common event and is associated with a poor outcome. The objective of this study was to investigate the prevalence and risk factors associated with the diagnosis of distant metastasis in oral and oropharyngeal carcinoma patients. The medical charts of 2327 patients treated from 1954 to 1997 were reviewed. They were 1703 patients (73.2%) with oral cavity and 624 (26.8%), oropharyngeal tumours. Regarding the primary treatment: 637 patients (27.4%) underwent surgery alone; 1147 (49.3%), radiotherapy alone and 543 (23.3%), combined treatment (surgery and radiotherapy). During the follow-up period after the initial treatment, 89 patients (3.8%) were diagnosed with distant metastasis. The variables associated with the distant metastasis-free survival were: tumour site (p=0.008); T stage (p<0.001); N stage (p<0.001); treatment performed (p<0.001) and decade of admission at the institution (p<0.001). The multivariate analysis (Cox regression) showed that the clinical stage (p=0.007); treatment performed (p=0.012) and decade of admission at the institution (p=0.004) were independent predictive factors for distant metastasis. Distant metastasis has been diagnosed more frequently in the latter decade and the significant predictors associated with its presence were the advanced clinical stage and patients who had undergone combined treatment.

Nuclear BAG-1 expression inhibits apoptosis in colorectal adenoma-derived epithelial cells

BAG-1 is an anti-apoptotic protein that is frequently deregulated in a variety of malignancies including colorectal cancer. There are three isoforms: BAG-1L is located in the nucleus, BAG-1M and BAG-1S are located both in the nucleus and the cytoplasm. In colon cancer, the expression of nuclear BAG-1 is associated with poorer prognosis and is potentially a useful predictive factor for distant metastasis. However, the function of BAG-1 in colonic epithelial cells has not been studied. Having previously shown a predominant nuclear localisation of BAG-1 in adenoma-derived cell lines, we wanted to determine the function of nuclear BAG-1 in these non-tumourigenic cells, to identify whether nuclear BAG-1 was implicated in tumour progression in the colon. In the current report we established that nuclear BAG-1 inhibits apoptosis in a colorectal adenoma-derived cell line. We demonstrate that apoptosis induced by gamma-radiation or the vitamin D analogue EB1089 in the non-tumourigenic human colorectal adenoma-derived S/RG/C2 cell line, was preceded by a decrease in nuclear and an increase in cytoplasmic BAG-1 expression. This change in subcellular localisation of BAG-1 was due to the redistribution of the BAG-1M isoform. In addition, we have shown that the maintenance of high nuclear BAG-1 through enforced expression of the nuclear localised BAG-1L isoform enhanced cellular survival after gamma-radiation or exposure to EB1089. Furthermore the expression of cytoplasmic BAG-1S isoform fused with a nuclear localisation signal protected against gamma-radiation induced apoptosis. This demonstrates that nuclear localisation of the BAG-1 protein confers a survival advantage in colorectal adenoma-derived cells and that nuclear BAG-1 could potentially be an important survival factor in colorectal carcinogenesis.

Nuclear BAG-1 expression reflects malignant potential in colorectal carcinomas.

BAG-1 is a recently identified Bcl-2-interacting anti-apoptotic protein. The aim of our study was to investigate the immunohistochemical staining pattern of BAG-1 protein in patients with colorectal cancer and examine associations of BAG-1 expression with various clinicopathological factors and patient survival. Tumour samples were collected from 86 patients diagnosed with colorectal cancer. There was significant variation in the immunohistochemical staining patterns for BAG-1, including absent staining and staining of either the cytoplasm, nucleus or both. Twenty-one colorectal carcinomas (24.4%) exhibited a nuclear staining pattern whilst 56 (65.1%) exhibited cytoplasmic staining. The percentage of cases exhibiting nuclear BAG-1 positivity was significantly higher in distant metastasis-positive cases (55.6%) than in distant metastasis-negative cases (20.8%; P=0.036). Overall survival was significantly shorter for patients with tumours exhibiting BAG-1 positive nuclei than those with absent nuclear BAG-1-staining (P=0.011). In addition, the multivariate cox proportional hazard models indicated that nuclear BAG-1 expression was the only independent prognostic variable for mortality (P=0.013). These studies demonstrate that nuclear BAG-1 expression is a useful predictive factor for distant metastasis and a poor prognosis in patients with colorectal cancer.British Journal of Cancer (2002) 87, 1136–1139. doi:10.1038/sj.bjc.6600579 www.bjcancer.com© 2002 Cancer Research UK