molecular pathology of intraductal papillary mucinous neoplasms of the pancreas

Since the first description of intraductal papillary mucinous neoplasms(IPMNs)of the pancreas in the eighties,their identification has dramatically increased in the last decades,hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases.However,the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions.The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed.We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms,identifying some genes,molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy.The knowledge of molecular biology of IPMNs has impressively developed over the last few years.A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified,in pancreatic juice or in blood or in the samples from the pancreatic resections,but further researches are required to use these informations for clinical intent,in order to better define the natural history of these diseases and to improve their management.

A new prognostic histopathologic classification of nasopharyngeal carcinoma

Background:The current World Health Organization(WHO) classification of nasopharyngeal carcinoma(NPC) con?veys little prognostic information.This study aimed to propose an NPC histopathologic classification that can poten?tially be used to predict prognosis and treatment response.Methods:We initially developed a histopathologic classification based on the morphologic traits and cell differentia?tion of tumors of 2716 NPC patients who were identified at Sun Yat?sen University Cancer Center(SYSUCC)(training cohort).Then,the proposed classification was applied to 1702 patients(retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients(prospective validation cohort) from SYSUCC.The efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes.We used Cox proportional hazards models to estimate hazard ratios(HRs) with 95% confidence intervals(CI) for overall survival(OS).Results:The 5?year OS rates for all NPC patients who were diagnosed with epithelial carcinoma(EC;3708 patients),mixed sarcomatoid?epithelial carcinoma(MSEC;1247 patients),sarcomatoid carcinoma(SC;823 patients),and squamous cell carcinoma(SCC;253 patients) were 79.4%,70.5%,59.6%,and 42.6%,respectively(P < 0.001).In mul?tivariate models,patients with MSEC had a shorter OS than patients with EC(HR = 1.44,95% CI = 1.27–1.62),SC(HR = 2.00,95% CI = 1.76–2.28),or SCC(HR = 4.23,95% CI = 3.34–5.38).Radiochemotherapy significantly improved survival compared with radiotherapy alone for patients with EC(HR 49–0.75),and possibly for those with SCC(HR = 0.67,95% CI = 0.56–0.80),MSEC(HR = 0.58,95% CI = 0..74–1.28).= 0.63;95% CI = 0.40–0.98),but not for patients with SC(HR = 0.97,95% CI = 0Conclusions:The proposed classification offers more information for the prediction of NPC prognosis compared with the WHO classification and might be a valuable tool to guide treatment decisions for subtypes that are associ?ated with a poor prognosis.

Nasopharyngeal carcinoma with synchronous breast metastasis:A case report

BACKGROUND Recent reports have described cases of metachronous breast metastasis in patients with nasopharyngeal carcinoma.However,no similar cases of synchronous breast metastasis have been reported,and evidence that can be used to support the clinical diagnosis of stage IV nasopharyngeal carcinoma in patients with concurrent breast metastasis remains lacking.Therefore,additional evidence is required to elucidate the clinical characteristics of this condition and aid in the development of optimal management strategies.CASE SUMMARY We report the case of a 46-year-old woman who visited our hospital with a right breast mass as the first symptom.The first pathological biopsy report suggested triple-negative breast invasive carcinoma.Subsequent imaging revealed a nasopharyngeal mass.Further puncture biopsy of the nasopharyngeal mass,molecular pathological Epstein–Barr virus in situ hybridization,and immunohistochemistry confirmed the diagnosis of nasopharyngeal carcinoma with breast metastasis.The patient did not undergo a mastectomy and achieved complete remission after chemotherapy and radiotherapy.She continued to receive oral chemotherapy as maintenance therapy and experienced no recurrence or metastasis during the 6-month follow-up period.CONCLUSION This case report suggests that breast specialists should carefully rule out secondary breast cancers when diagnosing and treating breast masses.Furthermore,clinicians should aim to identify the pathological type of the tumor to obtain the most accurate diagnosis and prevent excessive diagnosis and treatment.

European vs 2015-World Health Organization clinical molecular and pathological classification of myeloproliferative neoplasms

The BCR/ABL fusion gene or the Ph^1-chromosome in the t(9;22)(q34;q11)exerts a high tyrokinase acticity,which is the cause of chronic myeloid leukemia(CML).The1990 Hannover Bone Marrow Classification separated CML from the myeloproliferative disorders essential thrombocythemia(ET),polycythemia vera(PV)and chronic megakaryocytic granulocytic myeloproliferation(CMGM).The 2006-2008 European Clinical Molecular and Pathological(ECMP)criteria discovered 3variants of thrombocythemia:ET with features of PV(prodromal PV),"true"ET and ET associated with CMGM.The 2008 World Health Organization(WHO)-ECMP and 2014 WHO-CMP classifications defined three phenotypes of JAK2^(V617F)mutated ET:normocellular ET(WHO-ET),hypercelluar ET due to increased erythropoiesis(prodromal PV)and ET with hypercellular megakaryocytic-granulocytic myeloproliferation.The JAK2^(V617F)mutation load in heterozygous WHO-ET is low and associated with normal life expectance.The hetero/homozygous JAK2^(V617F)mutation load in PV and myelofibrosis is related to myeloproliferative neoplasm(MPN)disease burden in terms of symptomaticsplenomegaly,constitutional symptoms,bone marrow hypercellularity and myelofibrosis.JAK2 exon 12mutated MPN presents as idiopathic eryhrocythemia and early stage PV.According to 2014 WHO-CMP criteria JAK2 wild type MPL^(515)mutated ET is the second distinct thrombocythemia featured by clustered giant megakaryocytes with hyperlobulated stag-horn-like nuclei,in a normocellular bone marrow consistent with the diagnosis of"true"ET.JAK2/MPL wild type,calreticulin mutated hypercellular ET appears to be the third distinct thrombocythemia characterized by clustered larged immature dysmorphic megakaryocytes and bulky(bulbous)hyperchromatic nuclei consistent with CMGM or primary megakaryocytic granulocytic myeloproliferation.

PVSG and WHO vs European Clinical,Molecular and Pathological Criteria for prefibrotic myeloproliferative neoplasms

The Polycythemia Vera Study Group(PVSG),World Health Organization(WHO) and European Clinical,Molecular and Pathological(ECMP) classifications agree upon the diagnostic criteria for polycythemia vera(PV) and advanced primary myelofibrosis(MF). Essential thrombocythemia(ET) according to PVSG and 2007/2008 WHO criteria comprises three variants of JAK2V617 F mutated ET when the ECMP criteria are applied. These include normocellular ET,hypercellular ET with features of early PV(prodromal PV),and hypercellular ET due to megakaryocytic,granulocytic myeloprolifera-tion(ET.MGM). Evolution of prodromal PV into overt PV is common. Development of MF is rare in normocellular ET(WHO-ET) but rather common in hypercellular ET.MGM. The JAK2V617 F mutation burden in heterozygous mutated normocellular ET and in heterozygous/homozygous or homozygous mutated PV and ET.MGM is of major prognostic significance. JAK2/MPL wild type ET associated with prefibrotic primary megakaryocytic and granulocytic myeloproliferation(PMGM) is characterized by densely clustered immature dysmorphic megakaryocytes with bulky(bulbous) hyperchromatic nuclei,which are never seen in JAK2V617 F mutated ET,and PV and also not in MPL515 mutated normocellular ET(WHO-ET). JAK2V617 mutation burden,spleen size,LDH,circulating CD34+ cells,and pre-treatment bone marrow histopathology are mandatory to stage the myeloproliferative neoplasms ET,PV,PMGM for proper prognosis assessment and therapeutic implications. MF itself is not a disease because reticulin fibrosis and reticulin/collagen fibrosis are secondary responses of activated polyclonal fibroblasts to cytokines released from the clonal myeloproliferative granulocytic and megakaryocytic progenitor cells in ET.MGM,PV and PMGM.

Pathological features and diagnosis of intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm(IPMN) of the pancreas is a noninvasive epithelial neoplasm of mucinproducing cells arising in the main duct(MD) and/or branch ducts(BD) of the pancreas.Involved ducts are dilated and filled with neoplastic papillae and mucus in variable intensity.IPMN lacks ovarian-type stroma,unlike mucinous cystic neoplasm,and is defined as a grossly visible entity(≥ 5 mm),unlike pancreatic intraepithelial neoplasm.With the use of high-resolution imaging techniques,very small IPMNs are increasingly being identified.Most IPMNs are solitary and located in the pancreatic head,although 20%-40% are multifocal.Macroscopic classification in MD type,BD type and mixed or combined type reflects biological differences with important prognostic and preoperative clinical management implications.Based on cytoarchitectural atypia,IPMN is classified into low-grade,intermediategrade and high-grade dysplasia.Based on histological features and mucin(MUC) immunophenotype,IPMNs are classified into gastric,intestinal,pancreatobiliary and oncocytic types.These different phenotypes can be observed together,with the IPMN classified according to the predominant type.Two pathways have been suggested:gastric phenotype corresponds to less aggressive uncommitted cells(MUC1-,MUC2-,MUC5 AC +,MUC6 +) with the capacity to evolve to intestinal phenotype(intestinal pathway)(MUC1-,MUC2 +,MUC5 AC +,MUC6- or weak +) or pancreatobiliary /oncocytic phenotypes(pyloropancreatic pathway)(MUC1 +,MUC 2-,MUC5 AC +,MUC 6 +) becoming more aggressive.Prognosis of IPMN is excellent but critically worsens when invasive carcinoma arises(about 40% of IPMNs),except in some cases of minimal invasion.The clinical challenge is to establish which IPMNs should be removed because of their higher risk of developing invasive cancer.Once resected,they must be extensively sampled or,much better,submitted in its entirety for microscopic study to completely rule out associated invasive carcinoma.

Intraductal papillary-mucinous neoplasia of the pancreas:Histopathology and molecular biology

Intraductal papillary-mucinous neoplasm(IPMN) of the pancreas is a clinically and morphologically distinctive precursor lesion of pancreatic cancer,characterized by gradual progression through a sequence of neoplastic changes.Based on the nature of the constituting neoplastic epithelium,degree of dysplasia and location within the pancreatic duct system,IPMNs are divided in several types which differ in their biological properties and clinical outcome.Molecular analysis and recent animal studies suggest that IPMNs develop in the context of a field-defect and reveal their possible relationship with other neoplastic precursor lesions of pancreatic cancer.

Epigenetic disruption of cell signaling in nasopharyngeal carcinoma

Nasopharyngeal carcinoma(NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia.Alternative to genetic changes,aberrant epigenetic events disrupt multiple genes involved in cell signaling pathways through DNA methylation of promoter CpG islands and/or histone modifications.These epigenetic alterations grant cell growth advantage and contribute to the initiation and progression of NPC.In this review,we summarize the epigenetic deregulation of cell signaling in NPC tumorigenesis and highlight the importance of identifying epigenetic cell signaling regulators in NPC research.Developing pharmacologic strategies to reverse the epigenetic-silencing of cell signaling regulators might thus be useful to NPC prevention and therapy.

Is nasopharyngeal cancer really a “Cantonese cancer”?

Nasopharyngeal cancer(NPC) is endemic in Southern China,with Guandong province and Hong Kong reporting some of the highest incidences in the world.The journal Science has called it a "Cantonese cancer".We propose that in fact NPC is a cancer that originated in the Bai-Yue("proto-Tai-Kadai" or "proto-Austronesian" or "proto-Zhuang") peoples and was transmitted to the Han Chinese in southern China through intermarriage.However,the work by John Ho raised the profile of NPC,and because of the high incidence of NPC in Hong Kong and Guangzhou,NPC became known as a Cantonese cancer.We searched historical articles,articles cited in PubMed,Google,monographs,books and Internet articles relating to genetics of the peoples with high populations of NPC.The migration history of these various peoples was extensively researched,and where possible,their genetic fingerprint identified to corroborate with historical accounts.Genetic and anthropological evidence suggest there are a lot of similarities between the Bai-Yue and the aboriginal peoples of Borneo and Northeast India;between Inuit of Greenland,Austronesian Mayalo-Polynesians of Southeast Asia and Polynesians of Oceania,suggesting some common ancestry.Genetic studies also suggest the present Cantonese,Minnans and Hakkas are probably an admixture of northern Han and southern Bai-Yue.All these populations have a high incidence of NPC.Very early contact between southern Chinese and peoples of East Africa and Arabia can also account for the intermediate incidence of NPC in these regions.

The results and prognosis of different treatment modalities for solitary metastatic lung tumor from nasopharyngeal carcinoma:a retrospective study of 105 cases

Background and Objective:Nasopharyngeal carcinoma (NPC) is known for its propensity for distant metastases.Lung metastasis is one of the most important causes of death for patients with NPC.Solitary metastatic lung tumor from NPC is a distinctive group associated with a better survival.This study was to find a more effective treatment modality and prognostic factors for the group.Methods:Clinical data of 105 cases of solitary metastatic lung tumor from NPC were retrospectively analyzed.Survival rate was calculated by the Kaplan-Meier method.The difference of survival between the patients treated by different modalities was evaluated by the log-rank test.The Cox univariate and multivariate analyses of gender, age, pathologic type, stage, adjuvant chemotherapy, evaluation of treatment for NPC, disease-free interval, size of metastatic tumor, pulmonary hilar and/or mediastinal lymph node metastasis, treatment modalities, recurrent distant metastases and/or relapse of NPC were conducted.Results:The local control rate was 53.8% in chemotherapy group, 88.0% in radiotherapy +/-chemotherapy group, and 96.4% in operation +/-chemotherapy group (P<0.01).The most promising progression-free survival (PFS) and overall survival (OS) were obtained with operation +/-chemotherapy and followed by radiotherapy +/-chemotherapy.Both of them showed much better efficacy than chemotherapy (P<0.001).The Cox multivariate analysis showed that recurrent distant metastases and/or relapse of NPC affected the survival (OR=2.087, 95% CI=1.277-3.410, P=0.003).The T stage of NPC, size of metastatic tumor, hilar and/or mediastinal lymph node metastasis, and the treatment modality were independent prognostic factors.Conclusions:Operation +/-chemotherapy and radiotherapy +/-chemotherapy are better treatment of solitary metastatic lung tumor from NPC, which could improve the local control and prolong the PFS and OS.Chemotherapy is recommended for patients with higher T stage of NPC, size of metastatic tumor ≥3 cm, pulmonary hilar and/or mediastinal lymph node metastasis.

Pretreatment platelet count improves the prognostic performance of the TNM staging system and aids in planning therapeutic regimens for nasopharyngeal carcinoma:a singleinstitutional study of 2,626 patients

Introduction:Thrombocytosis has been identified as an unfavorable prognostic factor in several types of cancer.This study aimed to evaluate the prognostic value of pretreatment platelet count in association with the TNM staging system and therapeutic regimens in patients with nasopharyngeal carcinoma(NPC).Methods:A total of 2,626 patients with NPC were retrospectively analyzed.Platelet count >300 × 10~9/L was defined as thrombocytosis.Matched-pair analysis was performed between patients receiving chemoradiotherapy and radiotherapy.Results:Multivariate analysis showed that platelet count was an independent unfavorable prognostic factor for overall survival(OS)[hazard ratio(HR) = 1.810,95%confidence interval(CI) = 1.531-2.140,P < 0.001]and distant metastasis-free survival(DMFS)(HR = 1.873,95%CI = 1.475-2.379,P < 0.001) in the entire patient cohort.Further subgroup analysis revealed that increased platelet count was an independent unfavorable prognostic factor for OS and DMFS in patients with NPC stratified by early and advanced T category,N category,or TNM classification(all P < 0.001).Receiver operating characteristic(ROC) curves verified that the predictive value of TNM classification for OS was improved when combined with pretreatment platelet count(P = 0.030).Matched-pair analysis showed that chemoradiotherapy significantly improved OS only in advanced-stage NPC with thrombocytosis(HR = 0.416,95%CI = 0.226-0.765,P = 0.005).Conclusions:Pretreatment platelet count,when combined with TNM classification,is a useful indicator for metastasis and survival in patients with NPC.It may improve the predictive value of the TNM classification and help to identify patients likely to benefit from more aggressive therapeutic regimens.

CT-guided needle biopsy through mandibular area for the diagnosis of nasopharyngeal carcinoma in the parapharyngeal space

Background and Objective: The primary submucous type of nasopharyngeal carcinoma (NPC) or the recurrent NPC in the parapharyngeal space is difficult to be diagnosed histologically by conventional biopsy because of the obstruction of the surrounding structures. This study was performed to evaluate the needle biopsy approach through the madibular area into the parapharyngeal space under the guidance of computed tomography (CT) for NPC. Methods: Between July 6, 2005 and October 23, 2009, a total of 6 patients were enrolled into the study. Two patients with cervical lymph node metastasis were clinically suspicious of NPC according to their clinical manifestations. However, no cancer cell could be found by repeated nasopharyngeal biopsies followed by histologic examinations. The other 4 patients were diagnosed with recurrent NPCs by magnetic resonance imaging (MRI) or/and positron emission tomography (PET)-CT scan, showing tumors in the parapharyngeal spaces in 3 patients and enlarged retropharyngeal lymph node in 1 patient. The CT-guided puncture was performed through the mandibular skin and the cutting needle biopsy was taken at the parapharyngeal space focus. Results: All the cutting needle biopsies of projected locations have been performed safely. Finally, all the 7 specimens met the requirement of pathologic diagnosis and the cases were all confirmed histologically to be NPCs. The main complication was mild ache at the puncture point. No blood vessel or nerve was injured and no patient needed special treatment. Conclusions: The CT-guided puncture biopsy of the parapharyngeal space through the mandibular area is simple and feasible. It can be an additional option for routine nasopharyngeal biopsy.

Relationship between traditional Chinese medicine syndrome differentiation and imaging characterization to the radiosensitivity of nasopharyngeal carcinoma

Background and Objective: Traditional Chinese medicine (TCM) is a well established and time-honored practice in China, employing syndrome differentiation as a basis for the treatment of disease. According to different TCM syndrome typing findings, combining modern medical methods with TCM approaches can improve the quality of life and comprehensive effect on patients with nasopharyngeal carcinoma (NPC). This study investigated the relationship between TCM syndrome typing and imaging characterization to radiosensitivity as to provide objective evidence for the integration of Chinese and modern medical approaches in the treatment of NPC. Methods: Prior to treatment, TCM syndrome typing, computed tomography (CT) and magnetic resonance imaging (MRI) were performed on 147 patients pathologically classified with NPC. The status of tumor remission was radiologically evaluated at accumulated doses of 20 Gy, 40 Gy and 60 Gy, and at 3 months after completion of radiotherapy. Statistical results were analyzed by the Friedman and K-W test procedures. Results: Prior to treatment, TCM syndrome typing of NPC included Lung Heat, Blood Stasis, Phlegm Congealment and Blood Stasis-Phlegm Congealment. Lung Heat typing accounted for the highest proportion at 34.7% (51/147), followed by Phlegm Congealment at 32.7% (48/147), Blood Stasis at 17.0% (25/147) and Blood Stasis-Phlegm Congealment at 15.7% (23/147). Radiological imaging demonstrated a higher incidence of cervical lymph node metastases in Phlegm Congealment and Blood Stasis-Phlegm Congealment types (P < 0.05), while Blood Stasis and Blood Stasis-Phlegm Congealment types were more prone to skull base invasion (P < 0.05). Residual tumor size was larger in Blood Stasis and Blood Stasis-Phlegm Congealment types than in Lung Heat and Phlegm Congealment types after 3 months of treatment (P < 0.05). Conclusions: Different radiological manifestations were observed in TCM syndrome typed NPC patients, with lesser radiosensitivity demonstrated in the Blood Stasis and the Blood Stasis-Phlegm Congealment types relative to the Lung Heat and Phlegm Congealment types.

The Comparison of Diagnostic Significance of Narrow Band Imaging in Contrast of White Light Endoscopy in the Assessment of Nasopharyngeal Cancer

Background: Narrow band imaging (NBI) is reported to improve the diagnostic importance of nasopharyngeal cancer. The purpose of this review was to evaluate the diagnostic significance of NBI in the literature and compare it to the conventional white light endoscopy. The use of narrow band imaging (NBI) and further technological achievements concerning the resolution and magnification of endoscopic images have in the past 15 years. With the use of NBI, superficial mucosal lesions, which may be missed by standard WLI endoscopy, can be identified easily by their neoangiogenic pattern. Objective:?To assess diagnostic value of the narrow band imaging and white light endoscopy in nasopharyngeal carcinoma and compare diagnostic values (sensitivity, specificity, positive predictive value and negative predictive value) with white light endoscopy. Search Methods: From 2010 to 2020, data was searched from electronic databases such as PubMed, web of science. We used narrow band imaging as a key word accordance with diagnostic modalities such as sensitivity, specificity, PPV and NPV and data were collected. Results: We have found mainly 6 studies have discussed about diagnostic value of endoscopy in nasopharyngeal carcinoma in the total of 2746 suspected patients. Among them, 5 studies have compared diagnostic values such as sensitivity, specificity, positive predictive value and negative predictive value between NBI and WLE. Among 5 studies, 4 studies have found higher sensitivity in NBI, 2 studies found higher 1 equal to WLE specificity in NBI. 3 studies have compared PPV and NPV between NBI and WLE. Among them, all the studies found higher PPV and NPV in NBI than WLE. Conclusion: Recently?developed narrow band imaging has a great significance in the diagnosis of nasopharyngeal carcinoma. Although NBI has also encountered some problem such as contact bleeding and darker image. So, further evaluation should be done.

Nasopharyngeal carcinoma in the Northeastern states of India

Nasopharyngeal cancer (NPC) is a rare disease in most parts of the world, except for Southeast Asia, some parts of North Africa and the Arctic. It is mostly seen in people of Chinese origin. In India, NPC is also rare, except for the Hill States of Northeast India, particularly Nagaland, Manipur, and Mizoram. The striking feature of NPC in Northeast India is that the incidence ranges over the complete spectrum from the lowest (as 0.5/100 000 to 2.0/100 000 among Caucasoid) to the highest (as ~20/100 000 among Cantonese/Zhongshan dialect Chinese). The age-adjusted rate of NPC in Kohima district of Nagaland State is 19.4/100 000, which is among the highest recorded rates. By contrast, in Assam, one of the so-called Hill States but not itself a hilly state, NPC is much less common. The Northeastern region is distinguished by a preponderance of the Tibeto-Burman languages and by variable mongoloid features among peoples of the region. The nature of the migratory populations who are presumed to be bearers of the mongoloid risk is unknown, but these NPC occurrence features provide an outstanding opportunity for NPC risk investigation, such as that of the hypothesis of Wee et al. for westward displacement of Chinese aborigines following the last glacial maximum.

On the trails of markers and proxies:the socio-cognitive technologies of human movement,knowledge assemblage,and their relevance to the etiology of nasopharyngeal carcinoma

Bacteria,pigs,rats,pots,plants,words,bones,stones,earrings,diseases,and genetic indicators of all varieties are markers and proxies for the complexity of interweaving trails and stories integral to understanding human movement and knowledge assemblage in Southeast Asia and around the world.Understanding human movement and knowledge assemblage is central to comprehending the genetic basis of disease,especially of a cancer like nasopharyngeal carcinoma.The problem is that the markers and trails,taken in isolation,do not all tell the same story.Human movement and knowledge assemblage are in constant interaction in an adaptive process of co-production with genes,terrain,climate,sea level changes,kinship relations,diet,materials,food and transport technologies,social and cognitive technologies,and knowledge strategies and transmission.Nasopharyngeal carcinoma is the outcome of an adaptive process involving physical,social,and genetic components.

Correlation of Skp2 overexpression to prognosis of patients with nasopharyngeal carcinoma from South China

S-phase kinase-associated protein 2 (Skp2), which plays a role in cell cycle regulation, is commonly overexpressed in a variety of human cancers and associated with poor prognosis. However, its role in nasopharyngeal carcinoma (NPC) is not well understood. In this study, we examined the clinical significance of Skp2, with a particular emphasis on overall survival (OS) and disease-free survival (DFS), in NPC cases in South China, where NPC is an epidemic. Additionally, we explored the function of Skp2 in maintaining a cancer stem cell -like phenotype in NPC cell lines. Skp2 expression was assessed for 127 NPC patients using tissue microarrays and immunohistochemistry and analyzed together with clinicopathologic features, OS, and DFS. Skp2 expression was detectable, or positive, in 75.6% of patients. Although there was no correlation between Skp2 and any clinicopathologic factor, Skp2 expression significantly portended inferior OS (P = 0.013) and DFS (P = 0.012). In the multivariate model, Skp2 expression remained significantly predictive of poor OS [P = 0.009, risk ratio (RR) = 4.06] and DFS (P = 0.008, RR = 3.56), and this was also true for clinical stage (P = 0.012 and RR=3.201 for OS; P = 0.002 and RR=1.94 for DFS) and sex (P = 0.016 and RR=0.31 for OS; P = 0.006 and RR = 0.27 for DFS). After Skp2 knockdown, a colony formation assay was used to evaluate the self-renewal property of stem-like cells in the NPC cell lines CNE-1 and CNE-2. The colony formation efficiency in CNE-1 and CNE-2 cells was decreased. In Skp2-transfected CNE-1 and CNE-2 cells, side population (SP) proportion was increased as detected by flow cytometry. Skp2 is an independent prognostic marker for OS and DFS in NPC. Skp2 may play a role in maintaining the cancer stem cell-like phenotype of NPC cell lines.

Detection of nasopharyngeal carcinoma using surface-enhanced laser desorption and ionization mass spectrometry profiles of the serum proteome

Background and Objective: Early diagnosis of nasopharyngeal carcinoma (NPC) is difficult due to the insufficient specificity of the conventional examination method. This study was to investigate potential and consistent biomarkers for NPC, particularly for early detection of NPC. Methods: A proteomic pattern was identified in a training set (134 NPC patients and 73 control individuals) using the surface-enhanced laser desorption and ionization-mass spectrometry (SELDI-MS), and used to screen the test set (44 NPC patients and 25 control individuals) to determine the screening accuracy. To confirm the accuracy, it was used to test another group of 52 NPC patients and 32 healthy individuals at 6 months later. Results: Eight proteomic biomarkers with top-scored peak mass/charge ratios (m/z) of 8605 Da, 5320 Da, 5355 Da, 5380 Da, 5336 Da, 2791 Da, 7154 Da, and 9366 Da were selected as the potential biomarkers of NPC with a sensitivity of 90.9% (40/44) and a specificity of 92.0% (23/25). The performance was better than the current diagnostic method by using the Epstein-Barr virus (EBV) capsid antigen IgA antibodies (VCA/IgA). Similar sensitivity (88.5%) and specificity (90.6%) were achieved in another group of 84 samples. Conclusion: SELDI-MS profiling might be a potential tool to identify patients with NPC, particularly at early clinical stages.

CHEMOTHERAPY FOR ADVANCED NASOPHARYNGEAL CARCINOMA WITH METHOTREXATE, VINCRISTINE, CISPLATIN AND ADRIAMYCIN

Objective: To evaluate the efficacy and toxicity of M-VCA (methortrexate 30 mg/m2, vincristine 2 mg, cisplatin 70 mg/m2, adriamycin 30 mg/m2) combination chemotherapy for advanced nasopharyngeal carcinoma. Methods: Thirty-five patients with advanced nasopharyngeal carcinoma, including 11 patients with untreated local advanced nasopharyngeal carcinoma and 24 patients with local-regional recurrent or metastatic nasopharyngeal carcinoma, received the chemotherapy of M-VCA. The cycle was repeated on day 22 for two cycles. All patients completed the chemotherapy courses. Results: The overall response rate was 75%, with untreated local advanced nasopharyngeal carcinomas 11/11(100%), local-regional recurrent nasopharyngeal carcinomas 12/18(67%), lung metastases 8/9(89%), bone metastases 5/9(56%), and liver metastases 1/2(50%). The main side effects included mild to moderate degree alopecia, nausea/vomiting, and neutropenia. Conclusion: M-VCA is well tolerated and has good efficacy for advanced nasopharyngeal carcinoma and is worth investigating further.

THREE-DIMENSIONAL CONFORMAL RADIATION THERAPY FOR LOCALLY RECURRENT NASOPHARYNGEAL CARCINOMA

Objective: To investigate the safety and effectiveness of three-dimensional conformal radiation therapy (3-D CRT) for locally recurrent nasopharyngeal carcinoma (NPC). Methods: From April 1998 to March 2000, 34 patients who had undergone previous external beam radiation therapy were retreated with 3-D CRT for locally recurrent NPC (33 poorly differentiated squamous cell carcinomas, 1 adenoma). The patients were re-staged according to Huaqing staging system with the following distribution: T1N0M0 in 5 cases, T2N0M0 in 11 cases, T3N0M0 in 12 cases, T4N0M0 in 6 cases. The maximal dimension of the gross tumor volume (GTV) ranged from 1.0 cm to 5.0 cm (median: 2.9 cm). CT simulation and 3-D planning were used to ensure full and conformal coverage of the planning target volume (PTV) by treated volume, while minimizing the absorbed dose of the adjacent normal tissue. 5–7 static conformal coplanar or noncoplanar portals were delivered for each fraction irradiation. The total dose delivered ranged from 65–70 Gy, with 2.5 Gy per fractionation, one fractionation per day, 5 days a week. Median follow-up time from 3-D CRT was 25 months (range: 12–36 months). Results: Over the follow-up period, local recurrence was observed in 3 patients, regional failure in 3, distant metastasis in 3, and six patients died; 88.2% (30/34) of the patient maintained local control, 82.4% (28/34) survived, and 76.5% (26/34) survived with no evidence of tumor. Acute complications were minor and few. The overall incidence of late complication was 20.6% (7/34), and severe complication was 14.7% (5/34), after re-irradiation with 3-D CRT. Conclusion: 3-D CRT is safety and effectiveness for most of the patients with locally recurrent NPC. Our preliminary results indicate a high local control rate and a low complication rate. The long-term curative effect and sequelae await further study.