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Wei Ju,1,2,* Guan-fa Luo,1,* Yuan-yuan Shi,3 Fei-jun Zhou,1 Meng-qi Li,1 Jian-hui Xu,1 Zhi-xin Yan,2 Xi-hu Yang1 1Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of China; 2Department of Burn and Plastic Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xi-hu Yang, Email yangxihu1981@126.comObjective: Sebaceous carcinoma (SC) of the submandibular gland is extremely rare. Owing to the low morbidity and nonspecific clinical manifestations, diagnosis is commonly delayed, which increases metastasis and mortality. To date, there have been five reported cases of SC of the submandibular gland. Here, we present a new case and review the relevant literature.Methods and Results: A 36-year-old woman presented with an enlarged left submandibular gland. Clinical features included a non-tender solitary nodular mass with normal overlying skin. There were no special findings on computed tomography or ultrasound examination except for a swollen mass in the left submandibular gland. The patient underwent surgical resection. Pathological examination confirmed the diagnosis of SC with nerve infiltration. Immunohistochemical examination of this case showed positive staining for P63, P40, CK7, CK8/18, MLH1, MSH2, MSH6, and PMS2. The specimen was negative for androgen receptor, CEA, S-100, CK5/6, SOX-10, SOX-11, SMA, and GCDFP-15. The KI-67 labeling index was determined to be 15%. PAS and anti-epithelial membrane antigen were positive in partial area. The patient is still undergoing follow-up, and no metastasis or recurrence has been observed for 2 months.Conclusion: This case highlighted the fact that despite its rarity, SC should be considered as a differential diagnosis for masses located in the head and face. Early and accurate diagnosis, followed by wide surgical excision, has a favorable prognosis. Therefore, clinicians should be familiar with the clinical and pathological features of this disease.Keywords: sebaceous carcinoma, salivary gland neoplasms, submandibular gland, androgen receptor, P63, P40

Luo Y, Liu F, Yan C, et al. Cancer Manag Res. 2020;12:2195–2207. We, the Editor and Publisher of Cancer Management and Therapy are retracting the published article. Since publication, concerns have been raised about the duplication of images in this article with those from other unrelated articles. Specifically, The image from Figure 2D, A498, si-NC, has been duplicated with the image from Figure 4C, C-33A, agomir-NC from Wu F, Sui Y, Wang Y, Xu T, Fan L, Zhu H. Long Noncoding RNA SNHG7, a Molecular Sponge for microRNA-485, Promotes the Aggressive Behavior of Cervical Cancer by Regulating PAK4. Onco Targets Ther. 2020;13:685–699. https://doi.org/10.2147/OTT.S232542 (RETRACTED). The image from Figure 5C, 786-O, si-NC, has been duplicated with the image from Figure 2D, H460, si-NC from Dai J, Wang B, Zhao Y, et al. RETRACTED ARTICLE: Long Noncoding RNA LINC01426 Sequesters microRNA-519d-5p to Promote Non-Small Cell Lung Cancer Progression by Increasing ETS1 Expression. Cancer Manag Res. 2020;12:12697–12708. https://doi.org/10.2147/CMAR.S277113 (RETRACTED). The image from Figure 5C, 786-O, si-CASC19+miR-532 inhibitor, and Figure 6E, 786-O, si-CASC19+pcDNA3.1-ETS1 has been duplicated with the image from Figure 6D, A549, agomiR-NC, and Figure 6E, A549, agomiR-NC, respectively, from Kang X, Kong F, Wu S, et al. microRNA-612 suppresses the malignant development of non-small-cell lung cancer by directly targeting bromodomain-containing protein 4. Onco Targets Ther. 2019;12:4167–4179. https://doi.org/10.2147/OTT.S204004 (RETRACTED). The image from Figure 5D, 786-O, si-CASC19+NC inhibitor, has been duplicated with the image from Figure 6F, Hep3B, 2, from Yun Z, Meng F, Jiang P, Yue M, Li S. microRNA-548b suppresses aggressive phenotypes of hepatocellular carcinoma by directly targeting high-mobility group box 1 mRNA. Cancer Manag Res. 2019;11:5821–5834.https://doi.org/10.2147/CMAR.S198615 (RETRACTED).The image from Figure 5D, A498, si-NC, has been duplicated with the image from Figure 5D, CAOV-3, miR-control from Li C, Yu S, Wu S, Ni Y, Pan Z. MicroRNA-936 targets FGF2 to inhibit epithelial ovarian cancer aggressiveness by deactivating the PI3K/Akt pathway. Onco Targets Ther. 2019;12:5311–5322. https://doi.org/10.2147/OTT.S213231 (RETRACTED) and Figure 5d, TPC-1, si-LINC00520+antagomir-577, from Sun Y, Shi T, Ma Y, Qin H, Li K. RETRACTED ARTICLE: Long noncoding RNA LINC00520 accelerates progression of papillary thyroid carcinoma by serving as a competing endogenous RNA of microRNA-577 to increase Sphk2 expression. Cell Cycle. 2020;19(7):787–800. DOI: https://doi.org/10.1080/15384101.2020.1731062 (RETRACTED). The image from Figure 6D, 786-O, si-CASC19+pcDNA3.1-ETS1, has been duplicated with the image from Figure 4D, Migration, HOS, agomir-760, from Yin R, Liu J, Zhao D, Wang F. Long Non-Coding RNA ASB16-AS1 Functions as a miR-760 Sponge to Facilitate the Malignant Phenotype of Osteosarcoma by Increasing HDGF Expression. Onco Targets Ther. 2020;13:2261–2274. https://doi.org/10.2147/OTT.S240022 (RETRACTED). The image from Figure 6E, A498, si-NC, has been duplicated with the image from Figure 2D, Eca109, si-NC, from Gao J, Zhang Z, Su H, Zong L, Li Y. Long Noncoding RNA FGD5-AS1 Acts as a Competing Endogenous RNA on microRNA-383 to Enhance the Malignant Characteristics of Esophageal Squamous Cell Carcinoma by Increasing SP1 Expression. Cancer Manag Res. 2020;12:2265–2278. https://doi.org/10.2147/CMAR.S236576 (RETRACTED). When approached for an explanation, the authors have been unable to address the concerns raised and have not been able to provide sufficient original data from their study. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The authors listed in this publication have been informed. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Tao Zhang,1,* Qin Liu,2,* Yingfan Zhu,1 Songfa Zhang,3 Qiaohua Peng,3 Amanda Louise Strickland,4 Wenxin Zheng,4,5 Feng Zhou2 1Department of Gynecology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pathology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA; 5Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA*These authors contributed equally to this workCorrespondence: Feng ZhouDepartment of Pathology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, 310006, People’s Republic of ChinaTel +86-571-89991702Fax +86-571-87061878Email fungchew@zju.edu.cnPurpose: Programmed death-ligand 1 (PD-L1) has been widely used as a prognostic biomarker and an immunotherapeutic target in numerous cancers, but information on the clinical significance of its expression in endometrial serous carcinoma (ESC) is largely lacking. Here, we evaluate the predictive value of PD-L1 expression in ESC.Materials and Methods: A total of 79 cases of ESC accessioned between January 2003 and September 2015 were selected for further analysis. PD-L1 expression was evaluated in whole tissue sections of these cases by using the tumor proportion score (TPS, cut-off 1%) and combined positive score (CPS, cut-off 1) scoring methods.Results: Overall, there was a heterogeneous expression of PD-L1, focal or patchy, in ESCs. PD-L1 positivity was observed in 43.0% of ESCs by TPS and 73.4% of ESCs by CPS. Kaplan–Meier survival analysis showed that patients with PD-L1-positive tumors suffered significantly worse OS and PFS, when compared with PD-L1 negative tumors (log-rank p = 0.037 and p = 0.003, respectively). In contrast, PD-L1 positivity by CPS within the ESC cases showed no statistical significance for OS and PFS (log-rank p = 0.720 and p = 0.928, respectively). Multivariate Cox analysis showed that PD-L1 positivity by TPS was significantly associated with PFS (HR = 1.921, p = 0.039) but not OS (HR = 1.229, p = 0.631).Conclusion: PD-L1 expression is frequently found in ESC, suggesting a potential role of the PD-1/PD-L1 pathway as a potential therapeutic target for these tumors. PD-L1 expression by TPS also serves as a negative prognostic marker in ESC and implies an unfavorable outcome.Keywords: PD-L1, endometrial serous carcinoma, endometrial cancer, immune therapy

Qin Liu,1,&ast; Xin Zhou,1,&ast; Xiaofei Zhang,1 Amanda Louise Strickland,2 wenxin zheng,3 Hao Chen,3 Feng Zhou1 1Department of Pathology, Zhejiang University School of Medicine Women’s Hospital, Hangzhou, 310006, People’s Republic of China; 2Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611, USA; 3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75235, USA&ast;These authors contributed equally to this workCorrespondence: Feng ZhouDepartments of Pathology, Zhejiang University School of Medicine Women’s Hospital, Hangzhou, 310006, People’s Republic of ChinaTel +86-0571-89991702Email fungchew@zju.edu.cnHao ChenDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75235, USATel +1-469-419-1538Email Hao.Chen@UTSouthwestern.eduPurpose: To investigate the prevalence of precancers [high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS)] and cancers [squamous cell carcinoma (SCC) and adenocarcinoma (ADC)] in various high-risk human papillomavirus (hrHPV) genotypes or age groups among women with negative for intraepithelial lesion or malignancy (NILM) and hrHPV-positive pap results.Materials and Methods: In total, 26,228 women with NILM/hrHPV+ were included in the study. Among them, 5893 had immediate follow-up biopsy results available and were selected for further prevalence analysis.Results: About 7.6% and 0.7% women with NILM/hrHPV+ had HSIL and AIS, respectively. The prevalence of HSIL+ squamous lesions is significantly higher in HPV-16+ group than that in other genotype groups (p < 0.0001). The prevalence of AIS+ glandular lesions is significantly higher in HPV-18/45+ groups than women in other genotype groups (p < 0.0001). In addition, the prevalence of HSIL+ lesions was significantly higher in age 25– 39 years group than that in age 40– 65 years group and > 65 years group (p < 0.0001). Overall, the prevalence of HSIL+ in younger women was significantly higher than that in older women when using a cutoff age of 40 years (9.3% vs 5.9%, p < 0.0001) or 50 years (8.6% vs 4.9%, p < 0.0001). No significant difference in AIS+ prevalence was found among different age groups (p = 0.611). Interestingly, the prevalence of SCC and ADC in older women (≥ 40 years, 0.3% and 0.3%, respectively) was significantly higher than that in younger women (< 40 years, 0% and 0.07%) (p = 0.001 for SCC; p = 0.02 for ADC).Conclusion: The significant risk of cervical precancers and cancers still exists in women with NILM/hrHPV+, notably the older patient group had a lower risk of cervical precancer, but higher risk of cancer. Therefore, HPV genotyping can be an effective supplemental tool to cytology, and patient age also needs to be considered in the clinical management of patient.Keywords: risk stratification, E6/E7 mRNA genotyping, NILM, hrHPV

Menglei Zhang,1,2,* Fangyue Zhou,1,* Yuan He,3 Xiang Tao,4 Keqin Hua,1,2 Jingxin Ding1,2 1Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of China; 2Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, People’s Republic of China; 3Public Health School of Fudan University, Shanghai, 200032, People’s Republic of China; 4Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingxin DingDepartment of Gynecology, The Obstetrics and Gynecology Hospital of Fudan University, 128 Shen-Yang Road, Shanghai, 200011, People’s Republic of ChinaTel +86-13918206746Fax +86-21-63455090Email djxdd@sina.comPurpose: This study aimed to establish a predictive model for lymph node involvement (LNI) in patients with borderline ovarian tumor (BOT) using clinicopathological factors.Patients and Methods: We collected clinical data from consecutive patients who underwent lymphadenectomy for BOT between 2001 and 2018 and analyzed their clinicopathological features. Multivariate logistic regression was used to identify all independent risk factors associated with LNI; these were then incorporated into the prediction model.Results: In total, we included 248 patients with BOT who were undergoing lymphadenectomy. These were divided into a training cohort (n=174) and a validation cohort (n=74). When considering histopathological data, 16 and 5 patients were identified to have LNI in the training and validation cohorts, respectively. Overall, 13.5% (21/156) patients with serous BOT had LNI while 0% (0/92) patients with non-serous BOT had LNI. We identified several predictors of LNI: the largest tumor being ≥ 12.2cm in diameter, the presence of lesions on the ovarian surface, and the presence of pelvic or abdominal lesions. We created a prediction model and nomogram that incorporated these three risk factors for serous BOT. The model achieved good discriminatory abilities of 0.951 and 0.848 when predicting LNI in the training and validation cohorts, respectively. The LNI-predicting nomogram had an area under curve (AUC) of 0.951 and generated well-fitted calibration curves.Conclusion: Non-serous BOT may not require lymphadenectomy as part of surgical staging. The individual risk of LNI in patients with serous BOT can be accurately estimated using our prediction model and nomogram. The use of LNI criteria provides a practical way to support the clinician in making an optimal decision relating to surgical scope for patients with BOT.Keywords: lymph node involvement, borderline ovarian tumor, lymphadenectomy, prediction model, nomogram

Feng Zhou,1,2 Xiaofei Zhang,1 Hao Chen,2 Wenxin Zheng2– 4 1Department of Pathology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA; 3Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA; 4Harold C Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center, Dallas, TX, USACorrespondence: Feng ZhouDepartments of Pathology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of ChinaTel +86-571-89991702Email fungchew@zju.edu.cnPurpose: To investigate the relationship between dedifferentiated endometrioid carcinomas with neuroendocrine differentiation and mismatch repair deficiency.Patients and Methods: The clinicopathological records and samples of three patients were retrieved from the Pathology Department of Zhejiang University’s School of Medicine Women’s Hospital.Results: The tumors comprised one dominant poorly differentiated component (60– 90% of the neoplasm volume) and one well-differentiated glandular component. The poorly differentiated component showed solid sheets with organoid growth patterns and insular, trabecular and rosette/pseudorosette patterns. Large polygonal cells, vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm were observed in the poorly differentiated area. All three cases were diffusely positive for p16 and for at least two of three neuroendocrine markers (chromogranin, synaptophysin, neural cell adhesion molecule (CD56)) in > 10% of cancer cells. Loss of MMR protein expression was found in two patients: MLH1 and PSM2 in patient 2 and MSH2 and MSH 6 in patient 3. Abnormal P53 and SMARCB1 (INI1) expression was noted in patient 3. All three patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, and two received postoperative chemotherapy and/or radiation therapy. The patients survived disease-free for 60, 26 and 15 months, respectively.Conclusion: Dedifferentiated endometrioid carcinomas with neuroendocrine differentiation may be associated with mismatch repair deficiency and have an improved prognosis.Keywords: dedifferentiated endometrioid carcinoma, large cell neuroendocrine carcinoma, MMR deficiency

Luo Y, Liu F, Yan C, et al. Cancer Manag Res. 2020;12:2195–2207. The Editor and Publisher of Cancer Management and Research wish to issue an Expression of Concern for the published article. Following publication, concerns were raised were raised about the scientific integrity of the articles content. We reached out to the authors requesting they supply information that would confirm the integrity of the data. However, the authors did not respond to our queries or provide the requested files to confirm the authenticity of the data. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. The authors have been notified about this Expression of Concern.

Linglong Chen,1 Yaru Zhan,2 Fei He,3 Shouhua Zhang,3 Lin Wu,2,4 Honghan Gong,2,4 Fuqing Zhou,2,4 Xianjun Zeng,2,4 Haibo Xu1 1Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang 330006, People’s Republic of China; 3Department of Hematology, Jiangxi Provincial Children’s Hospital, Nanchang, 330000, People’s Republic of China; 4Jiangxi Medical Imaging Research Institute, Nanchang 330006, People’s Republic of ChinaCorrespondence: Haibo XuDepartment of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaEmail xuhaibo1120@hotmail.comHonghan GongDepartment of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of ChinaEmail 2805794252@qq.comObjective: Using functional connectivity density (FCD) mapping measured by resting-state functional magnetic resonance imaging (rs-fMRI), an ultrafast data-driven graph theory approach, we attempted to study the abnormalities in neural activity of young survivors of acute lymphoblastic leukemia (ALL) and to explore the neuropathological evidence of chemotherapy-related cognitive impairment of patients.Methods: Twenty young survivors of ALL and 18 well-matched healthy controls (HCs) were recruited in this study. All ALL patients and healthy controls underwent rs-fMRI scans and completed neurocognitive testing. The between-group differences in short-range and long-range FCD were calculated by the option of degree centrality (DC) in MATLAB software after preprocessing. The correlations between the FCD value and each of the neurocognitive outcomes were analyzed in the ALL patients.Results: The group-averaged FCD maps showed similar spatial patterns between the two groups. Compared with the HCs, ALL patients showed decreased long-range FCD in regions of the bilateral lingual gyrus, cingulate cortex, hippocampal gyrus, and right calcarine fissure. Simultaneously, decreased regions in the short-range FCD map were the bilateral lingual gyrus, cingulate cortex, parahippocampal gyrus and right calcarine fissure. Increased functional connectivity (FC) was observed between the region with decreased long-range FCD and the posterior cerebellar lobe, and decreased FC was observed between the region and the middle occipital gyrus, cuneus and lingual gyrus. Thus, there existed no brain areas with increased FCD. The decreased short-range FCD value of ALL patients was positively correlated with the score on the Digit Span Test (Forward), and the increased FC value was negatively correlated with the score on the Trail Making Test part A.Conclusion: Our results suggest the altered functional connectivity of young survivors of ALL in the posterior region of the brain and posterior lobe of the cerebellum. Alterations in spontaneous neuronal activity seem to parallel the neurocognitive testing, which indicates that the rs-fMRI could be used as a neuroimaging marker for neurological impairment in ALL patients.Keywords: acute lymphoblastic leukemia, resting-state fMRI, functional connectivity density, chemotherapy-related cognitive impairment, executive function

Fachen Zhou,1,2,* Jin Wang,2,* Xinming Chi,3 Xin Zhou,3 Zhou Wang1 1Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Department of Histology and Embryology, Dalian Medical University, Dalian, Liaoning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhou WangDepartment of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwuweiqi Road, Jinan, Shandong Province 250021, People’s Republic of ChinaTel +86 53 168777893Email wangzhoushandong@163.comXin ZhouDepartment of Histology and Embryology, Dalian Medical University, No. 9 West Part of Lvshun South Road, Dalian, Liaoning Province, People’s Republic of ChinaTel +86 41 186110314Email 18642818055@163.comPurpose: Metastasis is a crucial cause of the high mortality in patients with lung cancer. Long non-coding RNAs (lncRNAs) are emerging as important players in the development and progression of human cancers. Here, we aimed to identify metastasis-associated lncRNA and to study its roles in the migration and invasion of lung cancer cells.Materials and Methods: We screened differentially expressed lncRNAs between high- and low-metastatic lung cancer cell lines by using microarray and identified the target lncRNA TM4SF1-AS1. The effect of the TM4SF1-AS1 on the invasion and migration was evaluated through the wound healing experiment and transwell assay. The expression of related genes was assessed by RNA sequence and Western blotting.Results: TM4SF1-AS1 was highly expressed in high metastatic lung cancer cell line, and it was also significantly up-regulated in lymph node metastatic lung cancer and was associated with lymph node metastasis. Overexpression of TM4SF1-AS1 promoted the migration and invasion of lung cancer cells. Overexpression of TM4SF1-AS1 decreased the expression of E-Cadherin and increased the expression of Vimentin, Snail and Twist, while knockdown of TM4SF1-AS1 exhibited the opposite trend. Furthermore, RNA sequence analysis revealed that some signaling pathways, including PI3K/AKT signaling pathway, were enriched upon TM4SF1-AS1 overexpression. Western blotting further confirmed that the PI3K/AKT signaling pathway was activated by TM4SF1-AS1.Conclusion: This study illustrates that TM4SF1-AS1 promotes the migration and invasion of lung cancer cells by activating the PI3K/AKT signaling pathway. TM4SF1-AS1 might be a novel target of molecular treatment for lung cancer.Keywords: lung cancer, long non-coding RNA, TM4SF1-AS1, metastasis, PI3K/AKT signaling pathway

Ya Sun,1,2,* Shuo Yang,3,* Erpeng Qi,1 Fangyi Liu,1 Fubo Zhou,1 Yuhan Lu,1 Ping Liang,1 Huiyi Ye,4 Xiaoling Yu1 1Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, People’s Republic of China; 2Department of Ultrasound, Aerospace Central Hospital, Beijing 100049, People’s Republic of China; 3Chinese PLA Medical School, Beijing, 100853, People’s Republic of China; 4Radiology Department, Chinese PLA General Hospital, Beijing 100853, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoling YuDepartment of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, People’s Republic of ChinaEmail dyuxl301@aliyun.comPurpose: The purpose of our study was to evaluate the role of contrast-enhanced ultrasound (CEUS) with magnetic resonance imaging (MRI) and computed tomography (CT) in the pathological diagnosis of pancreatic cystic neoplasms (PCNs).Methods: A total of 90 patients (66 women, 24 men) aged 18– 71 years were studied prospectively. CEUS was performed in all patients, whereas MRI was performed in 85 patients and CT in 69 patients. We analyzed the sensitivity and accuracy of these three imaging modalities to diagnose the PCNs. Neoplasm size, location, shape, intralesional mural nodules, septa and duct dilatation were also assessed by different radiologists.Results: There were no significant differences in sensitivity for discriminating PCNs from pancreatic cystic lesions between CEUS and MRI (p=0.614) or between CEUS and CT (p=0.479). The diagnostic accuracy of CEUS for classifying PCNs was 64.4% (58/90), which was higher than that of CT (53.6%, 37/69, P=0.017), and lower than that of MRI (70.6%, 60/85, p=0.791). Regarding tumor size for lesions larger than 3 cm, CEUS was superior to CT in differentiating the specific type of PCN (p=0.041), and CEUS had the same value as MRI (p=0.774). Furthermore, CEUS is valuable for precisely characterizing internal structures, for instance, septa (p=0.003, compared with CT; p=0.443, compared with MRI) and nodules (p= 0.018, compared with CT; p=0.033, compared with MRI). The number of septa (p=0.033) and cyst morphology (p=0.016) were meaningful indicators in differentiating serous and mucinous adenoma. There was no significant difference in evaluating size and detecting duct dilatation among the three imaging methods.Conclusion: CEUS compares favorably with MRI in displaying the inner structure of PCNs and offers advantages over CT. CEUS can contribute in an important way to the diagnosis of pancreatic cystic neoplasms.Keywords: contrast-enhanced ultrasound, computed tomography, magnetic resonance imaging, pancreatic cystic neoplasms, diagnostic evaluation

Yu Luo, Feng Liu, Chunhui Yan, Wei Qu, Liang Zhu, Zheng Guo, Fan Zhou, Wei Zhang Department of Urology, The 161st Hospital of the People’s Liberation Army, Wuhan, Hubei 430010, People’s Republic of ChinaCorrespondence: Feng LiuDepartment of Urology, The 161st Hospital of the People’s Liberation Army, No. 68, Huangpu Road, Wuhan, Hubei 430010, People’s Republic of ChinaEmail liufwh@163.comPurpose: The long non-coding RNA cancer susceptibility 19 (CASC19) is recognized as an important regulator in gastric cancer, colorectal cancer, and non-small cell lung cancer. Nevertheless, to the best of our knowledge, the expression status and detailed roles of CASC19 in clear cell renal cell carcinoma (ccRCC) have not been elucidated. Hence, we aimed to determine CASC19 expression in ccRCC and investigate its roles in ccRCC oncogenicity. The molecular mechanisms underlying CASC19 functions in ccRCC were also determined.Methods: CASC19 expression was measured by using reverse transcription-quantitative polymerase chain reaction. The effects of CASC19 on ccRCC cell proliferation, colony formation, migration, and invasiveness in vitro, as well as on tumor growth in vivo, were examined by the MTT assay, colony formation assay, cell migration and invasiveness assays, and tumor xenograft in nude nice, respectively.Results: CASC19 was overexpressed in ccRCC tissues and cell lines. High expression of CASC19 was closely associated with unfavorable clinicopathological parameters and predicted negative clinical outcomes in patients with ccRCC. Knockdown of CASC19 decreased ccRCC cell proliferation, colony formation, migration, and invasiveness, as well as attenuated tumor growth in vivo. Mechanistically, CASC19 functioned as a competing endogenous RNA and upregulated the expression of ETS proto-oncogene 1 (ETS1) through sponging microRNA-532 (miR-532). Furthermore, rescue assays revealed that inhibiting miR-532 or restoring ETS1 expression partially abolished the impacts of CASC19 knockdown on ccRCC cells.Conclusion: The CASC19/miR-532/ETS1 regulatory pathway is crucial for the malignant manifestations of ccRCC, which makes it an attractive target for potential treatments of ccRCC.Keywords: cancer, MTT assay, cell migration, invasiveness, xenograft, knockdown

Jinrong Qiu, 1,* Fuping Zhou, 1,* Xinchun Li, 2,* Sufang Zhang, 2 Zhuo Chen, 2 Zenghui Xu, 2 Gaoxiong Lu, 2 Zhi Zhu, 3 Na Ding, 2 Jinxing Lou, 4 Zhenlong Ye, 2 Qijun Qian 1, 2, 4 1Department of Biotherapy, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University of Chinese PLA, Shanghai, People’s Republic of China; 2Shanghai Baize Medical Laboratory, Shanghai, People’s Republic of China; 3Department of Pathology, Changhai Hospital, The Second Military Medical University of Chinese PLA, Shanghai, People’s Republic of China; 4Shanghai Mengchao Cancer Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qijun Qian; Zhenlong YeShanghai Baize Medical Laboratory, Yuanguo Road, Shanghai 201805, People’s Republic of ChinaEmail qian@shcell.org; yezl@shcell.orgObjective: The evaluation of lymphocyte subsets is widely regarded as an important factor for monitoring tumor progression and response to therapy. This study was designed to establish a comprehensive and detailed assessment of peripheral lymphocyte subsets with a multi-parametric flow cytometry assay for response prediction and prognosis evaluation of cancer patients.Methods: Peripheral blood samples collected from 40 cancer patients and 23 age- and sex-matched healthy volunteers were tested for 29 lymphocyte subsets by flow cytometry. The univariate analysis was applied to establish the reference interval of healthy samples, and the ratio and proportion of 29 lymphocyte subsets between patient samples and healthy controls were compared to evaluate their clinical significance by Mann–Whitney U-test model.Results: The reference ranges of 29 lymphocyte subsets were established with a normal distribution and no significant differences were observed between genders. Compared with healthy control group, lower proportion and ratio of specific parameters, such as Naïve Th cells (p< 0.01), Naïve Tc cells (p< 0.01), CM (central memory) Tc cells (p< 0.01), Naïve T cells/Memory T cells (p< 0.001), Naïve T cells/EM (effector memory) T cells (p< 0.001) and Naive Th cells/Memory Th cells (p< 0.001), and higher proportion and ratio of EM Th cells (p< 0.001), EM Tc cells (p< 0.01), effector Tc cells (p< 0.05), EM Th cells/CM Th cells (p< 0.01) and EM Tc cells/CM Tc cells (p< 0.01), as well as Breg (p< 0.001), B cells (p< 0.05) and CD16-NK cells (p< 0.001) were found in cancer cohorts.Conclusion: This study suggests that the changes in certain lymphocyte subsets might be helpful to evaluate the immunity of cancer patients, and holds great potential for clinical application.Keywords: solid tumor, lymphocyte subsets, clinic significance, reference intervals, flow cytometry

Yu Qian,1,2,* Yuan Wu,3,* Zilong Yuan,4 Xiaohui Niu,5 Yaoyao He,4 Jun Peng,6 Fuxiang Zhou,1 Shaozhong Wei,7 Desheng Hu,3 Yunfeng Zhou1 1Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Medical Oncology, Hubei Cancer Hospital, Wuhan, Hubei, People’s Republic of China; 3Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan, Hubei, People’s Republic of China; 4Department of Radiology, Hubei Cancer Hospital, Wuhan, Hubei, People’s Republic of China; 5College of Informatics, Huazhong Agricultural University, Wuhan, Hubei, People’s Republic of China; 6Department of Pathology, Hubei Cancer Hospital, Wuhan, Hubei, People’s Republic of China; 7Department of Surgery, Hubei Cancer Hospital, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunfeng ZhouDepartment of Radiation and Medical Oncology, Zhongnan Hospital, 169 Donghu Road, Wuhan, Hubei, People’s Republic of ChinaTel +86 139 0715 4247Fax +86 27 6781 2892Email yfzhouwhu@163.comDesheng HuDepartment of Radiation Oncology, Hubei Cancer Hospital, 16 Zhuodaoquan S Road, Wuhan, Hubei, People’s Republic of ChinaTel +86 27 8767 0318Fax +86 27 8767 0151Email hds13907174495@163.comPurpose: Circulating tumour cells (CTCs) have been found to correlate with treatment response and prognosis in some cancers; however, such correlations have not been reported in nasopharyngeal carcinoma (NPC). We aimed to determine the relationship between CTCs and the treatment response in NPC.Patients and methods: In this prospective study, we ascertained the karyotype of CTCs and identified a possible correlation between karyotype and treatment response in locally advanced NPC (LANPC). We prospectively collected peripheral blood from LANPC patients. CTCs were measured by negative enrichment with immunofluorescence in situ hybridization (imFISH) and a centromere of chromosome 8 (CEP8) probe. Chromosome 8 was karyotyped in CTCs, which were identified as triploid, tetraploid or multiploid. Patients were then treated with platinum-based induction chemotherapy followed by concurrent chemoradiotherapy. CTCs were measured before and after treatment.Results: We detected CTCs in 27 of 50 (54%) patients, which served as a baseline value. The results were independent of age, smoking history and NPC clinical stage. All of the 27 evaluable enrolled patients with detectable CTCs showed decreases in both total CTCs and CTCs of different ploidies after treatment (P

Pei Lu, Minyi Xu, Zhongbo Xiong, Fangfang Zhou, Lei Wang Department of Clinical Laboratory, Shanghai No. 8 People’s Hospital, Shanghai, China Correspondence: Pei Lu; Lei WangDepartment of Clinical Laboratory, Shanghai No. 8 People’s Hospital, No. 8, Caobao Road, Xuhui District, Shanghai 200235, ChinaTel +86 21 3428 4588; +86 21 3428 4588Email lu_pei@sohu.com;wolei6610@126.com Objective: Chemotherapy failure derived from drug resistance is the most important reason causing the recurrence in colorectal cancer patients. Therefore, it is necessary to shed light on the mechanism of chemotherapy resistance in colorectal cancer patients.Methods: We looked into the contribution of Fusobacterium nucleatum and ANO1 to chemoresistance in the human colorectal carcinoma cell lines. We silence and overexpress ANO1 in HCT116 and HT29 cells with lentivirus and siRNA knockdown technique in the absence or presence of F. nucleatum, oxaliplatin or 5-fluorouracil (5-FU). ANO1, p-pg, cleaved PARP, cleaved caspase-3, and EGFR expression was measured by Western blot. Cell apoptosis was measured by flow cytometry.Results: We found that F. nucleatum promoted ANO1 expression on colon cancer cells. Moreover, ANO1 prevent colon cancer apoptosis from oxaliplatin and 5-FU. Additionally, knockdown ANO1 expression could block F. nucleatum protective effects and increase the apoptosis effects induced by oxaliplatin and 5-FU. Therefore, F. nucleatum might be biologically involved in the development of colon cancer chemoresistance via ANO1 pathway.Conclusions: Taken together, our findings provide a valuable insight into clinical management and therapy, which may ameliorate colorectal cancer patient outcomes. Keywords: colorectal cancer, F. nucleatum, chemoresistance, 5-fluorouracil, oxaliplatin, ANO1

Wenyong Tan,1,2 Ming Yang,3 Hongli Yang,2 Fangbin Zhou,2 Weixi Shen1 1Department of Oncology, Shenzhen Hospital of Southern Medical University, Shenzhen, People’s Republic of China; 2Clinical Medical Research Center, The Second Clinical Medical College (Shenzhen People Hospital), Jinan University, Shenzhen, People’s Republic of China; 3Shenzhen Jingmai Medical Scientific and Technique Company, Shenzhen, People’s Republic of China Abstract: Neoadjuvant therapy (NAT) has been used increasingly in patients with locally advanced or early-stage breast cancer. However, the accurate evaluation and prediction of response to NAT remain the great challenge. Biomarkers could prove useful to identify responders or nonresponders, or even to distinguish between early and delayed responses. These biomarkers could include markers from the tumor itself, such as versatile proteins, genes, and ribonucleic acids, various biological factors or peripheral blood cells, and clinical and pathological features. Possible predictive markers could also include multiple features from functional imaging, such as standard uptake values in positron emission tomography, apparent diffusion coefficient in magnetic resonance, or radiomics imaging biomarkers. In addition, cells that indirectly present the immune status of tumor cells and/or their host could also potentially be used as biomarkers, eg, tumor-infiltrating lymphocytes, tumor-associated macrophages, and myeloid-derived suppressor cells. Though numerous biomarkers have been widely investigated, only estrogen and/or progesterone receptors and human epidermal growth factor receptor have been proven to be reliable biomarkers to predict the response to NAT. They are the only biomarkers recommended in several international guidelines. The other aforementioned biomarkers warrant further validation studies. Some multigene profiling assays that are commercially available, eg, Oncotype DX and MammaPrint, should be used with caution when extrapolated to NAT settings. A panel of combined multilevel biomarkers might be able to predict the response to NAT more robustly than individual biomarkers. To establish such a panel and its prediction model, reliable methods and extensive clinical validation are warranted. Keywords: breast cancer, drug therapy, biomarker, predictive factor

Guozeng Xu,1,2,* Yuehan Zhou,3,* Fuxiang Zhou1,2 1Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China; 2Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan, China; 3Department of Pharmacology, Guilin Medical University, Guilin 541004, Guangxi, China *These authors contributed equally to this work Introduction: Chemokines are closely related with tumor immunity, progression, and metastasis. We aimed to construct a multi-RNA classifier of chemokine family genes for predicting tumor recurrence in stage I–III patients with colorectal cancer (CRC) after operation. Patients and methods: By analyzing microarray data, the Cox regression analysis was conducted to determine survival-related chemokine family genes and develop a multi-RNA classifier in the training set. The prognostic value of this multi-RNA classifier was further validated in the internal validation and external independent sets. Receiver operating characteristic curves were used to compare the prediction ability of the combined model of this multi-RNA classifier and stage, and this multi-RNA classifier and stage alone. Results: Nine survival-related chemokines were identified in the training set. We identified a nine-chemokine classifier and classified the patients as high-risk or low-risk. Compared with CRC patients with high-risk scores, CRC patients with low-risk scores had longer disease-free survival in the training (HR=2.353, 95% CI=1.480–3.742, P0.05) sets. This nine-chemokine classifier may only be applied in Marisa’s C2, C5, and C6 subtypes patients. Conclusion: Our nine-chemokine classifier is a reliable prognostic tool for some specific biological subtypes of CRC patients. It might contribute to guide the personalized treatment for high-risk patients. Keywords: classifier, colorectal cancer, chemokine, survival analysis, risk classification, microarray

Qiang-Hua Zhou,1,2,* Chuang-Zhong Deng,1,* Jie-Ping Chen,1 Kang-Bo Huang,1,2 Ting-Yu Liu,1,2 Kai Yao,1,2 Zhuo-Wei Liu,1,2 Zi-Ke Qin,1,2 Yong-Hong Li,1,2 Sheng-Jie Guo,1,2 Yun-Lin Ye,1,2 Fang-Jian Zhou,1,2 Wenlin Huang,1,3 Ran-Yi Liu,1 Hui Han1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; 2Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China; 3Guangdong Provincial Key Laboratory of Tumor Targeted Drugs, Guangzhou Enterprise Key Laboratory of Gene Medicine, Guangzhou Doublle Bioproducts Co. Ltd., Guangzhou, China *These authors contributed equally to this work Purpose: Molecular biomarkers, especially serologic factors, have been widely applied in cancer diagnosis and patient follow-up. However, there are few valuable prognostic factors in penile squamous cell carcinoma (PSCC). Here, the authors investigated whether laminin gamma 2 (LAMC2) expression, especially serum LAMC2 (sLAMC2) level, was a suitable prognostic factor that could aid in the prediction of survival in PSCC.Patients and methods: This study included 114 PSCC patients. Reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect LAMC2 expression; enzyme-linked immunosorbent assays were used to test sLAMC2 concentration; and a Transwell assay and an in vivo experiment in nude mice were used to test PSCC cell migration, invasion, and metastasis. The chi-squared test was used to analyze the association between LAMC2 level and clinical parameters, the Cox proportional hazards regression model was used to evaluate the hazard ratio for death, and Kaplan–Meier analysis with a log-rank test was used for the survival analysis.Results: LAMC2 was overexpressed in PSCC tissues, and the LAMC2 expression level was higher in metastatic lymph node (LN) tissues than in primary cancer tissues; moreover, the LAMC2 levels in primary cancer tissues and sLAMC2 were higher in patients with LN metastasis than in those without LN metastasis. Upregulated LAMC2 facilitated the migration, invasion, and epithelial-to-mesenchymal transition of PSCC cells in vitro and promoted LN metastasis of PSCC cells in nude mice. Elevated LAMC2 levels were strongly correlated with advanced clinicopathologic parameters, especially LN metastasis, in PSCC patients and predicted shorter disease-specific survival. The predictive value of sLAMC2 is superior to that of C-reactive protein and squamous cell carcinoma antigen previously reported in PSCC patients, and a stratification analysis revealed that the level of sLAMC2 had a higher predictive value for disease-specific survival in early penile cancer (especially at the N0/X stage) than in later-stage penile cancer.Conclusion: These findings suggest that sLAMC2 is a potential serologic prognostic marker in PSCC and could aid in risk stratification in early-stage PSCC patients. Keywords: penile neoplasms, serum markers, laminin, gamma 2, neoplasm metastasis

Fangbin Zhou,1,2 Yaying Zhou,3 Ming Yang,1 Jinli Wen,3 Jun Dong,4 Wenyong Tan1 1Department of Oncology, The Second Clinical Medical College, Shenzhen People’s Hospital, Jinan University, Shenzhen, People’s Republic of China; 2Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, People’s Republic of China; 3Clinical Medical Research Center, The Second Clinical Medical College, Shenzhen People’s Hospital, Jinan University, Shenzhen, People’s Republic of China; 4Department of Pathophysiology, Key Laboratory of the State Administration of Traditional Chinese Medicine, Medical College of Jinan University, Guangzhou, People’s Republic of China Background: Circulating endothelial cells (CECs) and their subpopulations could be potential novel biomarkers for various malignancies. However, reliable enumerable methods are warranted to further improve their clinical utility. This study aimed to optimize a flow cytometric method (FCM) assay for CECs and subpopulations in peripheral blood for patients with solid cancers.Patients and methods: An FCM assay was used to detect and identify CECs. A panel of 60 blood samples, including 44 metastatic cancer patients and 16 healthy controls, were used in this study. Some key issues of CEC enumeration, including sample material and anticoagulant selection, optimal titration of antibodies, lysis/wash procedures of blood sample preparation, conditions of sample storage, sufficient cell events to enhance the signal, fluorescence-minus-one controls instead of isotype controls to reduce background noise, optimal selection of cell surface markers, and evaluating the reproducibility of our method, were integrated and investigated. Wilcoxon and Mann–Whitney U tests were used to determine statistically significant differences.Results: In this validation study, we refined a five-color FCM method to detect CECs and their subpopulations in peripheral blood of patients with solid tumors. Several key technical issues regarding preanalytical elements, FCM data acquisition, and analysis were addressed. Furthermore, we clinically validated the utility of our method. The baseline levels of mature CECs, endothelial progenitor cells, and activated CECs were higher in cancer patients than healthy subjects (P

Hua Bai, Wen-Hui Wang, Fan-Fan Zhou, Dan Yang, Rui-Jun Li Department of Oncology, People’s Hospital of Zhengzhou, Zhengzhou, People’s Republic of ChinaCorrespondence: Rui-Jun Li, Department of Oncology, People’s Hospital of Zhengzhou, No. 33, Huanghe Road, Jin-Shui District, Zhengzhou, 450053, People’s Republic of China, Tel +86 13838508075, Email liruijunzy@163.comObjective: Therapeutic regimens are relatively scarce among patients with treatment-refractory metastatic colorectal cancer (CRC). This study aimed to determine the feasibility and tolerability of anlotinib plus PD-1 blockades in patients with treatment-refractory metastatic CRC retrospectively.Methods: A total of 68 patients with previously treated metastatic CRC who received anlotinib plus PD-1 blockades in clinical practice were included in this study retrospectively. Demographic and clinical characteristics of the patients, therapeutic outcomes and safety profile during administration were collected and briefly analyzed. All subjects were followed up regularly. Therapeutic outcomes, including drug response and prognosis, were presented, and a safety profile was depicted to illustrate the adverse reactions.Results: A total of 68 patients with treatment-refractory metastatic CRC who received anlotinib plus PD-1 blockades in clinical practice were included in the final analysis. Best therapeutic response during treatment indicated that partial response was observed in 11 patients, stable disease was noted in 41 patients, and progressive disease was found in 16 patients, producing an objective response rate of 16.2% (95% CI: 8.4%– 27.1%) and a disease control rate of 76.5% (95% CI: 64.6%– 85.9%). Prognostic analysis suggested that the median progression-free survival (PFS) of the 68 patients was 5.3 months (95% CI: 3.01– 7.59), and the median overall survival (OS) was 12.5 months (95% CI: 9.40– 15.60). Of the 11 patients who responded, the median duration of response was 6.7 months (95% CI: 2.89– 10.53). Safety profile during treatment showed that patients experienced adverse reactions regardless of grade, and grade ≥ 3 adverse reactions were found in 61 patients (89.7%) and 41 patients (60.3%), respectively. Common adverse reactions were hypertension, myelosuppression (including leukopenia, neutropenia, thrombocytopenia, and anemia), fatigue, and hand-foot syndrome.Conclusion: Anlotinib plus PD-1 blockades demonstrated encouraging efficacy and acceptable safety profile in patients with treatment-refractory metastatic CRC preliminarily in clinical practice. This conclusion should be confirmed in prospective clinical trials.Keywords: colorectal cancer, anlotinib, PD-1 blockades, efficacy, safety

Zi-Shan Lin,1,* Xiao-Juan Yu,1,* Xu Zhang,1,2 Su-Xia Wang,1,2 Xi-Nan Cen,3 Fu-De Zhou,1 Ming-Hui Zhao1,4 1Renal Division, Department of Medicine, Peking University First Hospital; Institute of Nephrology, Peking University, Renal Pathology Center, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, People’s Republic of China; 2Laboratory of Electron Microscopy, Pathological Centre, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Hematology, Peking University First Hospital, Beijing, People’s Republic of China; 4Peking-Tsinghua Center for Life Sciences, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fu-De ZhouRenal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University; Renal Pathology Center, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of ChinaTel +86-13501162527Fax +86-10-83575694Email zhoufude1801@vip.sina.comBackground: Monoclonal immunoglobulin-associated renal lesions in patients with newly diagnosed myeloma vary. We aimed to determine the pathological spectrum and analyze associated prognostic factors.Methods: Fifty-six patients with newly diagnosed multiple myeloma and biopsy-proven renal lesions were enrolled. Kidney biopsies were reanalyzed, and the baseline clinical characteristics, treatments and outcomes were recorded.Results: Fifty-one patients had monoclonal immunoglobulin-associated renal lesions, with myeloma cast nephropathy (MCN) being the most common pattern. We divided our cohort into pure MCN, MCN+ other pathologies and non-MCN. Patients with MCN had more severe renal injury than those with non-MCN. In our cohort, none of the patients with pure MCN or MCN + other pathologies presented with nephrotic syndrome. Patients with non-MCN had better renal and overall survival than those with pure MCN but similar survivals to those with MCN + other pathologies. Number of myeloma casts (HR 1.08, p = 0.012) was the only independent prognostic factor for renal survival. Male sex (HR: 3.64; p = 0.015) and number of casts (HR: 1.17; p = 0.001) were independent prognostic factors for overall survival.Conclusion: Patients with MCN had more severe renal injury than those with non-MCN. Patients with non-MCN had better renal and overall outcomes than those with pure MCN, but their outcomes were similar to those with MCN + other pathologies. The independent predictors of overall survival were male sex and number of myeloma casts.Keywords: kidney biopsy, multiple myeloma, myeloma cast nephropathy, monoclonal immunoglobulin, prognosis