RASSF1A and KRAS Expression in Oral Leukoplakia with Dysplasia and in Squamous Cell Carcinoma

Author(s):  
Costa V ◽  
◽  
El Achkar VNR ◽  
Ribeiro MP ◽  
Tristao SS ◽  
...  

The aim of this study is to investigate the role of RASSF1A and KRAS protein immunoexpression in Oral Leukoplakia with Epithelial Dysplasia (OLD) and in Oral Squamous Cell Carcinoma (OSCC). Immunohistochemical staining for RASSF1A and KRAS was performed and a semiquantitative analysis was applied to samples of the Control Group (CG, n=20), OLD (n=39), and OSCC (n=100). No significant difference was observed between RASSF1A immunoexpression and OLP and OSCC groups (p>0.05). KRAS expression was higher in OSCC than in OLP and CG (p<0.05). No association was observed between RASSF1A or KRAS expression and alcohol/tobacco use or clinicopathological features (p>0.05) in the OSCC group. Also, patients with OSCC who presented KRAS overexpression had a worse disease-free survival rate (p=0.04). RASSF1A expression was similar in OLD and OSCC groups, suggesting that it plays a critical role in the early stage of OSCC. KRAS expression was higher in OSCC when compared with normal and dysplastic tissues, showing that KRAS expression increases with malignant progression.

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Karolina Gołąbek ◽  
Krzysztof Biernacki ◽  
Jadwiga Gaździcka ◽  
Joanna K. Strzelczyk ◽  
Katarzyna Miśkiewicz-Orczyk ◽  
...  

Oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) are subgroups of head and neck squamous cell carcinoma. E2F Transcription Factor 2 (E2F2) could contribute to cancer development, because it plays a critical role in many cellular processes, including the cell cycle, proliferation, differentiation, DNA damage response, and cell death. In the current study, we assessed the associations of five E2F2 polymorphisms (rs6667575, rs3218121, rs3218211, rs3218148, and rs3218203) with OSCC and OPSCC and influence on the TNM staging and grading. This is the first such survey to concern the European population. The study included 94 primary tumour samples following surgical resection from patients, whereas the control group consisted of 99 healthy individuals. We tried a matching of cases and controls for age and sample size. DNA samples were genotyped by employing the 5 ′ nuclease assay for allelic discrimination. Our results suggested that the most significant difference between the control group and the cancer group was the A/G heterozygote for rs3218121. Samples containing this genotype were mostly found in the control group. In our samples, rs6667575, rs3218121, rs3218211, and rs3218148 polymorphisms may affect the course of OSCC and OPSCC, while rs3218203 was not associated with OSCC and OPSCC. However, further studies are warranted to confirm our findings.


2020 ◽  
Vol 11 (SPL4) ◽  
pp. 1426-1431
Author(s):  
Archana Sonone ◽  
Alka Hande ◽  
Madhuri Gawande ◽  
Swati Patil

Tumour markers are biochemical substances released through tumour cells. They are considered as the rationale or consequence of the carcinogenesis process.  Neoplasms often have an increased concentration of sialic acid on the tumour cell surface and are shed or secreted by some of these cells, which increase the concentration in blood.  To determine serum levels of total sialic acid (TSA), lipid-bound sialic acid (LBSA), in patients of oral Leukoplakia (LP) and oral squamous cell carcinoma (OSCC). The study comprises 75 subjects which include 25 cases of LP, 25 cases of OSCC and 25 cases of healthy individuals as control. 10 ml intravenous blood was collected under aseptic condition, and biochemical analysis of total sialic acid and lipid-bound sialic acid was carried out by spectrophotometer. We observed levels of TSA and LBSA significantly increased in LP and OSCC as compared to a healthy control group. The increased level of TSA and LBSA in LP helps to determine the early stage of the disease. Further differentiation in grades of OSCC is also possible by these biochemical markers. Thus serum levels of TAS, LBSA can be used as diagnostic and prognostic markers.


2020 ◽  
Vol 30 (7) ◽  
pp. 969-974
Author(s):  
Liming Zhang ◽  
Hui Zhang ◽  
Yuheng Huang ◽  
Xiaowei Xi ◽  
Yunyan Sun

ObjectiveCervical cancer is one of the most common cancers worldwide, and immune function may impact disease progression. Serum markers may also be associated with diagnosis and progression. The aim of this study was to explore the clinical usefulness of determining the levels of peripheral blood immune cells and serum tumor markers in predicting diagnosis and prognosis of patients with cervical cancer.Methods82 patients with cervical cancer (early stage group: IA–IB1 and IIA1; locally advanced group: IB2 and IIA2), 54 patients with cervical intra-epithelial neoplasia (CIN), and 54 healthy women (control group) were recruited. Inclusion criteria were: (1) patients whose cervical lesions were determined based on biopsy; and (2) patients who had not undergone immunotherapy, chemotherapy, or radiotherapy. The exclusion criteria were as follows: (1) patients with a history of other malignant tumors; (2) patients with heart, kidney, and other organ failure; (3) patients with immune diseases; and (4) pregnant or lactating women. The levels of immunocytes and tumor markers were assayed. The relationships among histopathologic factors were analyzed. The correlation between the levels of immunocytes and tumor markers in patients with different degrees of cervical lesions (pre-invasive or cancer) and healthy women was evaluated.ResultsThe squamous cell carcinoma antigen and carcinoembryonic antigen levels in the control group and the CIN group were significantly lower than those in the cervical cancer groups (p<0.01). The incidence of lymph node metastasis in the early stage and locally advanced groups were 22.9% (11/48) and 46.2% (12/26), respectively, and 58.8% (20/34) and 7.5% (3/37) in the positive and negative lymphovascular invasion groups, respectively (p<0.05). The levels of CD8+ and CD8+ CD28+ T cells in the early stage group were markedly lower than those in the CIN group and the control group (p=0.014, p=0.008, respectively). The ratio of CD4+CD25+/CD4+ in the cervical cancer groups was significantly higher than in the control group (p<0.01). The increased serum squamous cell carcinoma and carcinoembryonic antigen levels and CD4+CD25+/CD4+ ratio were risk factors for cervical cancer by logistic regression analysis (p<0.05).ConclusionsIn patients with cervical cancer, immune function was impaired compared with that in healthy women and patients with CIN, while squamous cell carcinoma and carcinoembryonic antigen levels were increased. Combined detection of the levels of peripheral blood immune cells and serum tumor markers may be helpful for early detection, diagnosis, and prognosis evaluation of patients with cervical cancer.


2020 ◽  
Vol 21 (17) ◽  
pp. 6220
Author(s):  
Nima Attaran ◽  
Xiaolian Gu ◽  
Philip J. Coates ◽  
Robin Fåhraeus ◽  
Linda Boldrup ◽  
...  

Oral cancers are surrounded by epithelium that histologically might seem normal, but genetically has aberrations. In patients with squamous cell carcinoma of the oral tongue (SCCOT), it is therefore important to study not only the tumor but also the clinically tumor-free contralateral tongue tissue that remains in the patient after treatment to map changes of prognostic and/or diagnostic value. The transporter associated with antigen processing (TAP) dimer is a key factor in the process of activating cytotoxic T cells. By downregulating the expression of TAP, tumor cells can escape cytotoxic T cell recognition. Biopsies from tumor and clinically tumor-free contralateral tongue tissue in 21 patients with SCCOT were analyzed together with tongue biopsies from 14 healthy individuals, which served as the control group. Dividing patients into TAP1-high and TAP1-low groups according to the median TAP1 level in tumor-free samples showed that patients with lower TAP1 mRNA levels in tumor-free samples had better overall (p = 0.003) and disease-free survival (p = 0.002). The results showing that TAP1 levels in tumor-free tongue tissue contralateral to the SCCOT correlate with survival is an important contribution to early diagnosis and follow up of SCCOT.


1997 ◽  
Vol 106 (6) ◽  
pp. 445-450 ◽  
Author(s):  
Philip Grey ◽  
Prashant Chawla ◽  
Michael Friedman ◽  
T. K. Venkatesan ◽  
David D. Caldarelli ◽  
...  

This study was conducted to determine whether Bcl-2 overexpression in localized squamous cell carcinoma of the head and neck (SCCHN) might serve as a marker for tumors unlikely to respond to standard treatment. Tissue samples from 33 patients undergoing surgery or irradiation for early-stage SCCHN during the years 1977 to 1992 were stained for Bcl-2. All patients had either T1N0 lesions of the oral cavity, pharynx, or larynx or T1 NO or T2N0 lesions of the true vocal cords. Of the 33 patients, 26 remained disease-free after at least 3 years of follow-up; the remaining 7 patients developed either tumor recurrence or a second primary tumor, 4 of which were fatal. Twelve patients had tissue specimens staining positive for Bcl-2; 6 of these patients had a poor outcome, and 6 had a good outcome. The relationship between poor outcome and overexpression of Bcl-2 in tumor cells was statistically significant (p =.0047 by Fisher's exact test). For tumors overexpressing Bcl-2, there was no significant difference in recurrence rate between those undergoing surgery and those undergoing radiotherapy as the primary mode of treatment. The overexpression of Bcl-2 in early lesions in this study predicted a cure rate of 50%, as opposed to the generally expected 90%, suggesting that Bcl-2 is a significant prognostic indicator in early SCCHN. Future studies will determine if altering the treatment will improve outcome in these patients.


2013 ◽  
Vol 141 (5-6) ◽  
pp. 304-307 ◽  
Author(s):  
Marija Kostic ◽  
Nadja Nikolic ◽  
Branislav Ilic ◽  
Jelena Carkic ◽  
Sanja Milenkovic ◽  
...  

Introduction. Association studies have shown that gene polymorphisms in various classes of genes can modulate cancer risk. The -31G/C polymorphism in the promoter of survivin gene, affects the expression of the anti-apoptotic protein survivin which in turn may predispose an individual to some types of cancer. Objective. The aim of the study was to determine whether the survivin promoter -31G/C polymorphism could be a susceptibility factor for squamous cell carcinoma (SCC) of the oral cavity and basal cell carcinoma (BCC) of the skin. Methods. The DNA obtained from 88 patients with SCC, 60 patients with BCC and 111 healthy individuals was subjected to polymerase chain reaction-restriction fragment length polymorphism analysis (PCR- RFLP) in order to determine genotype and allele frequencies in patients and control groups. Logistic regression was used for cancer risk assessment. Results. The following distribution of genotypes was obtained: CC genotype 15% in the SCC group, 13% in the BCC group and 12% in controls; CG genotype 41% in SCCs, 35% in BCCs, 48% in controls; GG genotype 44% in SCCs, 52% in BCCs and 40% in controls. Allelic frequencies were as follows: G allele 0.65 in SCCs, 0.69 in BCCs and 0.64 in the control group; C allele 0.35 in SCCs, 0.31 in BCCs and 0.36 in the control group. There was no statistically significant difference in allele or genotype frequencies between the patients and controls (p>0.05). Conclusion. In Serbian population, -31G/C polymorphism in the promoter of the survivin gene cannot be considered as a risk factor for oral squamous cell carcinoma and skin basal cell carcinoma.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17571-e17571
Author(s):  
Il Seok Jeong ◽  
Matthew Kim ◽  
Anthony L. Nguyen ◽  
Huan Mo ◽  
Bruce Hayton ◽  
...  

e17571 Background: Squamous cell carcinoma of the head and neck (SCCHN) is currently the sixth most common cancer in the world and is linked to tobacco, alcohol and human papillomavirus (HPV). Cisplatin (Cs)-based concurrent chemoradiation is currently the standard treatment for locally advanced disease with a desire for organ preservation. In 2006, cetuximab (Cx) with radiation was approved as another option for this indication. We performed a single institute retrospective analysis to explore the difference in efficacy between Cs and Cx regimens with respect to P16 and smoking status. Methods: We retrospectively reviewed pts in Loma Linda University Medical Center (LLUMC) with locally advanced SCCHN who received concurrent chemoradiation with either Cx or Cs as first-line treatment from 2006 to present. We excluded patients with nasopharyngeal cancers, and patients having surgery as first line of treatment. Overall survival (OS) and disease free survival (DFS) with respect to p16 status and smoking status are the two primary endpoints. Results: Based on our study criteria, 115 out of 1545 screened pts qualified. The average age at diagnosis was 60 years. 75.7% were males and 24.3% were females. Median follow-up is 26 months. There are overall 55 DFS events and 23 OS events. Comparing between smokers (S, n = 44) and non-smokers (NS, n = 42), there is no significant difference in OS (NS: HR = 0.73 [0.28-1.92], p = 0.52) while the DFS was significantly better in the NS (NS: HR = 0.53 [0.29-0.98], p = 0.043). The overall median OS of the P16-pos pts (n = 49) is not reached while that of P16-neg pts (n = 12) is 36 mo (P16-neg: HR = 6.431 [1.71-24.13], p = 0.0058). The overall median DFS of the P16-pos pts is not reached while that of P16-neg pts is 6.5 mo (P16-neg: HR = 5.39 [2.32-12.54], p < 0.001). Overall, the median OS of Cx is 132 mo while that of Cs is not reached (Cs: HR = 0.38 [0.16-0.90], p = 0.027). The median DFS is 30 mo for Cs and 25 mo for Cx. Within P16-pos population, there are 4 OS events in Cx (n = 18) while 0 in Cs (n = 31)(p = 0.0062, favors Cs); there are 5 DFS events in Cx while 9 in Cs (Cs: HR = 1.17 [0.39-3.51], p = 0.78). The median OS and DFS for both groups are not reached. Conclusions: Our analysis of retrospective single institute data shows that positive P16 significantly associates with better OS. These findings are consistent with previous reports. Compared to Cx, the Cs regimen significantly associates with a better OS but not DFS in both overall and P16-pos populations.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8522-8522
Author(s):  
Shugeng Gao ◽  
Ning Li ◽  
Shunyu Gao ◽  
Qi Xue ◽  
Shuhang Wang ◽  
...  

8522 Background: Early stage non-small-cell lung cancer (NSCLC) could benefit from anti-programmed cell death-1 (PD-1) monotherapy; however, the survival profiles remain to be disclosed. Here, we presented the two-year follow-up outcomes from a phase 1b study of sintilimab, an anti-PD-1 inhibitor in the neoadjuvant setting of NSCLC. Methods: Treatment-naive pts with resectable NSCLC (stage IA–IIIB) received two cycles of sintilimab followed by surgical resection. Postoperative treatment of sintilimab was at the discretion of investigator. The primary endpoint was AE, and key secondary endpoints included major pathological response (MPR), disease free survival (DFS) rate of 1 year and 2 years, and overall survival (OS) rate of 2 years. Results: Among 40 enrolled pts, 36 (90%) underwent R0 resection and were included in the R0 resection population. By data cutoff (January 20, 2021), the median follow-up for DFS and OS for all the enrolled pts was 23.9 (IQR 20.5–24.4) months and 26.4 (IQR 24.2–29.0) months. A total of 12 (33.3%) pts experienced relapse, and 6 pts died. The 1-yr and 2-yr DFS rate was 91.7%/73.3%. The 2-yr OS rate for overall population and R0 population was 87.5%/91.7%, respectively. In the R0 resection population, the median DFS and OS were both not reached. Superior 2-year DFS rates were observed in pts who achieved MPR (MPR vs. Non-MPR: 86.7% vs. 63.8%). DFS of pts with non-squamous cell carcinoma tended to be shorter than that of pts with squamous cell carcinoma (HR 2.71 [95%CI 0.67–11.0], p=0.1479). Pts with tumor mutation burden (TMB) ≥10 mutations/Mb and PD-L1 tumor proportion score (TPS)≥50% tended to have a better 2-yr DFS rate compared to those with TMB<10 and TPS<50. [table] For the post-hoc event free survival (EFS) analysis, the same trend was observed with DFS among different subgroups, and patients with TMB ≥10 mutations/Mb had a significant improved EFS (HR 0.125[95% CI 0.02,1.03], P=0.0222). Conclusions: Anti-PD-1 monotherapy emerged to be a promising neoadjuvant therapeutic strategy for resectable NSCLC with improved clinical outcomes. MPR could serve as a surrogate efficacy biomarker in this setting. Clinical trial information: ChiCTR-OIC-17013726. [Table: see text]


2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Dong Xiao ◽  
Xiangyan Cui ◽  
Xin Wang

Abstract It is known that lncRNA PTCSC3 inhibits thyroid cancer and glioma and STAT3 promotes cancer development. We, in the present study, investigated the potential involvement of PTCSC3 in laryngeal squamous cell carcinoma (LSCC) and explored its interactions with STAT3. In the present study, we showed that plasma PTCSC3 was down-regulated in early stage LSCC patients, and the down-regulation of PTCSC3 separated in early stage LSCC patients from control group. LncRNA HOTAIR was up-regulated in early stage LSCC patients and was significantly and inversely correlated with PTCSC3 in LSCC patients. PTCSC3 overexpression led to the inhibition of HOTAIR, while PTCSC3 expression was not significantly affected by HOTAIR overexpression. PTCSC3 overexpression mediated the inhibited, while HOTAIR overexpression mediated the promoted proliferation of LSCC cells. However, cell invasion and migration were not significantly affected by PTCSC3 overexpression. In addition, HOTAIR overexpression reduced the inhibitory effects of PTCSC3 overexpression on cancer cell proliferation. Moreover, PTCSC3 overexpression mediated the down-regulation of STAT3 and STAT3 overexpression mediated the up-regulation of HOTAIR. Therefore, PTCSC3 may negatively interact with HOTAIR through STAT3 to inhibit LSCC cell proliferation.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Huang Jing ◽  
Wu Xiuhong ◽  
Yu Ying ◽  
Liao Zhenrong ◽  
Cheng Xiyun ◽  
...  

Abstract Objective This study aimed to evaluate the clinical outcomes for patients with stage IB2/IIA2 cervical squamous cell carcinoma treated with neoadjuvant chemotherapy combined with radical surgery. Methods A total of 68 patients with cervical squamous cell carcinoma were randomly divided into the experimental group (n = 35) and the control group (n = 33). The patients in the experimental group received paclitaxel plus cisplatin neoadjuvant chemotherapy for two cycles, then underwent radical hysterectomy and bilateral adnexectomy at 2 weeks post-chemotherapy. The control group only underwent radical hysterectomy and bilateral adnexectomy after the diagnosis of cervical squamous cell carcinoma. The toxic and side effects of chemotherapy in the experimental group were observed. Also, the operation method, operation time, blood loss, grade of wound healing, complications, and postoperative pathology were noted in the two groups. Primary foci and pelvic lymph node recurrence and distant metastasis were observed, and 3-year and 5-year survival rates were calculated. Results Only one patient in the experiment had grade III bone marrow suppression; no other grade III and IV chemotherapy toxic reactions were observed. The operation was successfully completed in all patients. The operation time, intraoperative blood loss, placement of the ureteral catheter, bladder injury, ureteric injury, postoperative urinary tub, pelvic drainage tube indwelling time, anal exhaust time, postoperative complications, and metastatic ratio of lymph nodes were not significantly different between the two groups (P > 0.05). The number of dissected lymph nodes, deep myometrial invasion, and vascular tumor emboli showed a significant difference in the experimental group compared with the control group (P < 0.05). The 3-year disease-free survival (82.9% vs 81.9%), 5-year disease-free survival (71.4% vs 60.6%), 3-year overall survival (91.4% vs 87.8%), and 5-year overall survival (82.9% vs 75.6%) were not statistically significantly different between the experimental group and the control group (P > 0.05). Conclusions Neoadjuvant chemotherapy in IB2/IIA2 stage cervical squamous cell carcinoma showed low toxic side effects. Radical surgery after chemotherapy is safe and feasible. It plays a coordinating role in reducing the tumor infiltration depth of the deep muscle layer and the incidence of vascular tumor emboli, reducing the use of postoperative adjuvant therapy, and improving the quality of life of patients, but does not improve the 3-year/5-year survival rate.


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