Stage Squamous Cell Carcinoma Research Articles

Profiling of microRNAs in actinic keratosis and cutaneous squamous cell carcinoma patients

Actinic keratosis (AK) is a common skin lesion often defined as premalignant with more evidence indicating it as early stage of cutaneous squamous cell carcinoma (cSCC). The AK may remain stable, transform towards incisive cSCC or in some cases revert spontaneously. Several different underlying conditions can increase risk of cSCC, however, advanced age represents major risk of AK and its progression towards cSCC indicating increased risk during chronological aging. Importantly, AK and cSCC are characterized by similar genetic profile, which lead researchers to search for novel biomarkers allowing early detection. As skin sampling is often invasive and causes scaring, in the current study, we investigated a novel approach to establish potential blood circulating genetic markers in patients diagnosed with AK and cSCC. Based on clinical diagnosis and dermoscopy, we recruited 13 patients with AK (divided into two groups: the first included patients with no more than three lesions, the second group included patients with at least ten lesions) and two additional individuals diagnosed with cSCC. Deep sequencing analysis of serum circulating miRNAs detected a total of 68 expressed miRNAs. Further analysis indicated 2 regulated miRNAs for AK cohort and 12 miRNAs for cSCC patients, while there were 26 miRNAs differentially regulated between cSCC and AK patients. There was also one commonly regulated miRNA between AK and cSCC patients and ten miRNAs that were regulated in cSCC when compared with both control and AK patients. We did not observe any differences between the AK groups. In conclusion, our analysis detected in circulation some miRNA that were previously recognized as important in AK, cSCC, and other type of skin cancer supporting this approach as potential non-invasive diagnosis of AK and cSCC.

A case report of right upper lung adenosquamous carcinoma resection following neoadjuvant targeted therapy

The patient was a middle-aged male smoker who had space-occupying lesions in the right upper lung, Positron emission tomography-computed tomography (PET-CT) suggested right upper lung cancer with multiple mediastinal lymph node metastases. Endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-GS-TBLB) performed in the bronchus of the right apical segment confirmed the lesion as squamous cell carcinoma. Neoadjuvant therapy was planned. Because genetic testing revealed the epidermal growth factor receptor (EGFR) L858R mutation, the possibility of adenosquamous carcinoma was considered. The patient was clinically diagnosed with right upper lung squamous cell carcinoma c-T3N2M0, stage IIIB, and PS 1 point. Dacomitinib was selected for the targeted therapy. Eight weeks after the initiation of treatment, efficacy was assessed as a partial response (PR), suggesting a possibility of R0 resection. After sufficient communication with the patient and his family members, on July 1, 2020, thoracoscopic radical resection of the right upper lung cancer was performed under general anesthesia. Postoperative pathology confirmed adenosquamous carcinoma, of which 80% were adenocarcinoma and 20% were squamous cell carcinoma; no tumor thrombus was seen in the interstitial vessels; and the tumor did not invade the visceral pleura. There was no cancerous infiltration in the bronchial stump of the right upper lung. The following were the results for lymph nodes submitted for examination: L2 (0/1), L4 (0/4), L7 (0/3), L8 (0/7), L10 (0/1), L11 (0/2) and L11 (frozen 0/1) showed no cancer metastasis. The postoperative diagnosis was as follows: adenosquamous carcinoma of the right upper lung p-T2N0M0, stage Ib. After surgery, 4 cycles of the GC (gemcitabine + carboplatin) chemotherapy regimen were given, with continued targeted therapy recommended for 2 years. The patient has been followed-up and is in good condition.

Stratifin in ocular surface squamous neoplasia and its association with p53.

Sunlight-induced p53 mutations are known to contribute towards increased risk of ocular surface squamous neoplasia (OSSN). Stratifin (14-3-3σ)/HEM (human epithelial marker) is a p53-mediated inhibitor of cell cycle progression and has been shown to be a target of epigenetic deregulation in various carcinomas. In the present study, Stratifin expression, its promoter methylation status as well as expression of mutant p53 in early and advanced AJCC stages (8th edition) of OSSN, was evaluated. Sixty-four OSSN [20 conjunctival intraepithelial neoplasia (CIN) and 44 squamous cell carcinoma (SCC)] patients were registered for this study, and they were followed up for 36-58 months (mean 48 ± 3.6). Immunoexpression of Stratifin and mutant p53 protein, mRNA expression of Stratifin by reverse transcription polymerase chain reaction (PCR) and methylation status of Stratifin by methylation-specific PCR, was undertaken. Hypermethylation of Stratifin promoter in 63% (40/64), loss of Stratifin expression in 75% (48/64) and downregulation of Stratifin mRNA in 61% (39/64) were observed. Stratifin hypermethylation was significantly associated with reduced disease-free survival in both early and advanced T stage SCC cases. Expression of mutant p53 expression was seen in 48% (31/64) OSSN cases. Of the 31 patients with mutant p53 expression, 87% (27/31) also demonstrated loss of Stratifin immunoexpression. A significant association was seen between mutant p53 expression and Stratifin loss (p = 0.01) in advanced T stage SCC cases. Hypermethylation of Stratifin gene and its reduced mRNA expression both are potential biomarkers for identifying high-risk OSSN patients. Aberrant methylation of Stratifin and simultaneous mutant p53 expression implicates involvement of p53-Stratifin mediated signalling pathway in the pathogenesis of OSSN.

The accuracy of ultrasound and magnetic resonance imaging for estimating thickness of oral tongue squamous cell carcinoma and influence of biopsy on those findings

AbstractIntroductionA squamous cell carcinoma of the oral cavity or mobile tongue represents the sixth most common type of cancer worldwide. Patient work‐up procedures vary among institutions, though generally include clinical, imaging, and histopathology examinations. This study had two aims: assess the accuracy of ultrasound (US) and magnetic resonance imaging (MRI) for evaluating tumor thickness of ventral tongue squamous cell carcinoma, and ascertain the effects of biopsy on imaging results.MethodsWe retrospectively examined the medical records of 69 patients diagnosed and treated for ventral tongue squamous cell carcinoma stage T1 or T2. We compared tumor thickness in US and MRI results with histological thickness measured using specimens obtained in a partial glossectomy.ResultsThe mean difference between thickness measured with MRI before the biopsy procedure and that of the pathological specimens was 0.28 mm while that between US imaging results before the biopsy and histologic thickness was 0.75 mm. Furthermore, following the biopsy, the mean difference between thickness shown by MRI and that of the histological specimens was 0.89 mm, and between US findings and histologic thickness was 2.67 mm. There was a positive correlation between thickness shown by MRI and US when performed before the biopsy and the pathological result.ConclusionsMRI and US results appear to have adequate accuracy for estimating the thickness of T1‐and T2 lesions of the tongue when scanning is performed prior to a biopsy procedure. Furthermore, the present findings confirm the clinical impression that inflammatory changes induced by a biopsy often alter later imaging findings.

The Association of Tumor Burden by 18F-FDG PET/CT and Survival in Vulvar Carcinoma.

The aim of this study was to assess the impact of 18F-FDG PET/CT metabolic parameters obtained at initial staging of vulva carcinoma on survival in women with and without HIV infection. 18F-FDG PET/CT images of women with vulva cancer who are planned for definitive therapy were analyzed. SUVmax, SUVmean, MTV, and total lesion glycolysis (TLG) as well as whole-body MTV and whole-body TLG were computed. Twenty-five women were included with a mean age of 43.44 ± 10.32. The majority of the patients were HIV infected with a median CD4 count of 444.00 cells/mm3. The HIV-infected women are younger at diagnosis than their HIV-uninfected counterparts. All patients presented with inguinofemoral lymph node involvement, whereas half the patients had pelvic nodal metastasis. All the patients with distant visceral or skeletal metastasis were HIV infected. The lungs were the most common site of distant metastasis. When comparing the SUVmax, SUVmean, MTV, TLG, wbMTV, and wbTLG between HIV-infected and HIV-uninfected patients, we did not find statistical differences. Twelve patients (48%) were upstaged to metastatic disease. Seven patients had died at the time of analysis. The wbMTV and wbTLG were significantly higher in nonsurvivors than survivors. 18F-FDG PET/CT improves initial staging of squamous cell carcinoma among women with and without HIV infection. The whole-body tumor burden assessed by 18F-FDG PET metabolic metrics did not differ between HIV-infected and HIV-uninfected women. A higher whole-burden tumor burden is associated with a higher risk of mortality among women with vulva cancer.

Relationship of depth of invasion to survival outcomes and patterns of recurrence for T3 oral tongue squamous cell carcinoma

IntroductionCurrent research is elucidating how the addition of depth of invasion (DOI) to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging for oral cavity squamous cell carcinoma influences its prognostic accuracy. However, there is limited research on survival in pT3N0M0 oral tongue SCC (OTSCC) patients when stratifying by DOI. ObjectivesDetermine 5-year overall survival (OS), and cancer-specific survival (CSS) for patients with pT3N0M0 oral OTSCC based on shallow DOI (<10 mm) and deep DOI (10–20 mm). MethodsRetrospective review involving three tertiary care cancer centers in North America. cT3N0M0 OTSCC patients receiving primary surgical treatment from 2004 to 2018 were identified. Inclusion: age > 18 years old and confirmation of pT3N0M0 OTSCC on surgical pathology. Exclusion: patients undergoing palliative treatment or previous head and neck surgery/radiotherapy. Analysis comprised two groups: shallow pT3 (tumor diameter > 4 cm, DOI < 10 mm) and deep pT3 (DOI 10 mm-20 mm). ResultsOne hundred and four patients with pT3N0M0 OTSCC were included. Mean age was 59.1 years (range: 18–80.74). Age, gender, and Charlson Comorbidity Index were similar between the two groups (p > 0.05). Recurrence, LVI, PNI, and positive margins were more common in deep T3 tumors (P < 0.05). 5-year OS (50% vs 26%, p = 0.006) and CSS (72% vs 24%, p = 0.005) were worse in deep pT3 tumors. Deep pT3 disease was an independent predictor of OS (p = 0.004) and CSS (p = 0.01) on Cox-Regression analysis. ConclusionDOI is an independent predictor of poor survival in pT3N0M0 OTSCC patients. Consideration should be given to escalating adjuvant therapy for deep pT3N0M0 OTSCC patients.

Role of contrast enhanced computed tomography in assessing cervical lymph node metastases in oral cavity squamous cell carcinoma.

To evaluate the diagnostic accuracy of contrast-enhanced computed tomography scan in detecting cervical nodal metastasis in oral cavity squamous cell carcinoma. The retrospective cross-sectional study was conducted at Aga Khan University Hospital, Karachi, Pakistan. and comprised records from January 1, 2015, to October 31, 2016, of patients diagnosed with oral cavity squamous cell carcinoma and who underwent surgical resection of primary tumour along with neck dissection after having a contrast-enhanced computed tomography scan of head and neck. Diagnostic accuracy of the scans was calculated using final histopathology as the gold standard. All scans were reviewed by a consultant radiologist. Data was analysed using SPSS 23. Of the 100 patients whose records were reviewed, 70(70%) were female, 55(55%) had buccal and 32(32%) had tongue cancer.. The scans had sensitivity 83%, specificity 61.7%, positive predictive value 70.9%, negative predictive value 76.3% and overall diagnostic accuracy 73%. Computed tomography scan was found to be a useful tool for preoperative staging of oral cavity squamous cell carcinoma. However, due to low specificity and negative predictive value, elective neck dissection should still be done in a negative scan for cervical lymph node metastases.

Screening and validation of plasma long non-coding RNAs as biomarkers for the early diagnosis and staging of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC), characterized by a high recurrence rate, a poor prognosis and high morbidity, is the most prevalent malignancy of the oral cavity. The aberrant expression of long non-coding RNAs (lncRNAs) may lead to the development of various diseases, including cancer. Delayed diagnosis is the main reason for the poor prognosis. Therefore, the present study aimed to investigate the differential expression profiles of plasma lncRNAs in OSCC in order to screen target lncRNAs as biomarkers for the early diagnosis and staging of OSCC. The expression profiles of lncRNAs and mRNAs in OSCC were analyzed by microarray analysis. A total of 14 candidate lncRNAs were selected and analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) using the array homologous samples. Subsequently, 4 target lncRNAs were measured by RT-qPCR in a large cohort, including 28 cases with TNM I/II [early-stage squamous cell carcinoma (ESCC) group], 36 cases with TNM III/IV [advanced-stage squamous cell carcinoma (ASCC) group], 16 cases with dysplasia [oral premalignant lesion (OPL) group] and 16 healthy controls (H group). Receiver operating characteristic (ROC) curves and logistic regression analysis were used to evaluate the diagnostic effects of the combined lncRNAs. In total, 6,606 differentially expressed lncRNAs and 4,196 mRNAs were identified in OSCC. The expression trend of the 14 candidate lncRNAs was consistent with the microarray data. The expression level of ENST00000412740, NR_131012, ENST00000588803 and NR_038323 exhibited significant differences in the H, OPL, ESCC and ASCC groups (P<0.05). ROC curve and logistic regression analyses revealed that the diagnostic efficacy of the combined lncRNAs was more prominent than that of a single lncRNA, particularly in the ESCC and ASCC groups. In conclusion, the present study identified the differential expression profiles of plasma lncRNAs in OSCC and demonstrated that ENST00000412740, NR_131012, ENST00000588803 and NR_038323 may be promising biomarkers for the early diagnosis and staging of OSCC. These findings may provide novel targets for the early diagnosis and staging of OSCC, which may provide an objective basis for clinical decision-making.

Validation of the American Joint Committee on Cancer Staging in Squamous Cell Carcinoma of the Vermilion Lip.

The vermilion lip is a unique anatomical junction between cutaneous and mucosal surfaces. Squamous cell carcinoma (SCC) of the vermilion lip (vlSCC) was previously classified as oral SCC (oSCC) under the American Joint Committee on Cancer (AJCC) 7th edition (AJCC7), but has been recategorized as a cutaneous SCC of the head and neck (HNcSCC) in the AJCC 8th edition (AJCC8). We investigated the locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) for the various pathological T categories and disease stages of vlSCC as per AJCC8. We performed a retrospective cohort study of 297 patients diagnosed with vlSCC between January 2004 and February 2019. For this study, vlSCC cases were staged according to both AJCC7 and AJCC8. Kaplan-Meier survival curves and Cox regression models were used to analyze differences in LRC, DFS, and OS between each pT category and disease stage, and log-rank tests were performed for subgroup analysis. Restaging of vlSCC using the AJCC8 resulted in 19% of patients being upstaged to pT3, and 16% being upstaged to stage III. No patients were downstaged in pT stage or overall stage. Our study shows that when the AJCC8 HNcSCC staging system is applied to vlSCC, there are important aberrations leading to unwarranted upstaging of pT1 and redundancy of pT2. Understanding of these limitations are important in considering treatment escalation.

Predicting the risk of tumor progression in patients with early stages of adenocarcinoma and squamous cell lung carcinoma based on laboratory parameters

Non-small cell carcinoma (NSCLC) prevails in the structure of the incidence of lung cancer. In patients with I stage NSCLC, only 60-70% overcome the 5-year survival barrier, and at II stage it decreases to 35-40%. The reason for such a high mortality rate is almost always a relapse of the disease. The main histological forms of NSCLC - adenocarcinoma (AC) and squamous cell carcinoma (SCLC) - differ in the course, protocols and effectiveness of the treatment. Comparative survival data for AK and PCLC are controversial, and reliable biomarkers for determining the risk of tumor progression are lacking. In thus study we have investigated the possibility of using laboratory parameters characterizing the level of some blood proteins involved in carcinogenesis in patients with early stages of AC and SCLC to determine the risk of disease progression. We retrospectively analyzed the duration of the relapse-free period after surgical treatment for one year in 1250 patients (816 with stages I and II of adenocarcinoma, G1-3 and 434 with early stages of SCLC, G1-3). In 81 patients with AC and 36 - with SCLC (stages I-II, G1-3) the level of CYFRA 21-1 and SCC by electrochemiluminescent method, chemokines CXCL5, CXCL8, TPA, pyruvate kinase M2, HIF-1α and hyaluronic acid by enzyme immunoassay, receptors CXCR1, CXCR2, CD44v6 by flow cytometry were determined. Using the Kaplan-Meier graphical analysis, groups of low (stage I G1-2 + stage II G1) and high (stage I G3 + stage II G2-3) risk of tumor progression were identified. In the case of the one-year survival rate of patients with AC was higher than with SCLC. In patients with AC and a high risk of tumor recurrence, compared with a low one, the level of CYFRA 21-1, the mean intensity of fluorescence (MFI) of the CXCR1 receptor in granulocytes, and the relative content of the CXCR2 receptor in lymphocytes were higher. In the case of rapid progression of SCLC in patients, the relative content of the CXCR2 receptor in lymphocytes, the proportion of monocytes equipped with the CD44v6 receptor, and the SCC level were higher than with slow progression. Regression equations, including combinations of the above parameters (threshold value for AC - 0,512, for SCLC - 0,409, sensitivity - 91,9% and 90,0%, specificity - 90,0% and 87,5%, respectively), allow to predict the probability of tumor recurrence.

Impact of IL-10 Promoter Polymorphisms and IL-10 Serum Levels on Advanced Laryngeal Squamous Cell Carcinoma and Survival Rate.

Prognosis of advanced stages of laryngeal squamous cell carcinoma (LSCC) remains poor. To clarify therapeutic targets and improve survival rate, identification of new specific and prognostic biomarkers of LSCC is required. The study aimed to evaluate the impact of IL-10:rs1800871, rs1800872, rs1800896 single nucleotide polymorphisms (SNPs), and IL-10 serum levels on LSCC development and determine associations of selected SNPs with patient survival rate. A total of 300 LSCC patients and 533 controls were included in the study. Genotyping was carried out using RT-PCR; IL-10 serum levels were analyzed by ELISA. Significant associations were identified between IL-10 rs1800871 variants and advanced stage of LSCC patient group in the codominant, recessive and additive models (OR=0.473, p=0.027; OR=0.510, p=0.040; and OR=0.733; p=0.037). Significant variants of IL-10 rs1800872 were determined in the codominant, recessive and additive models (OR=0.473, p=0.027; OR=0.510, p=0.040; and OR=0.733, p=0.037). The distribution of IL-10 SNPs genotypes did not impact LSCC patient survival rate (respectively, p=0.952; p=0.952; p=0.991). IL-10:rs1800871 and rs1800872 SNPs are associated with advanced stage of LSCC. The genotypic distribution of IL-10 SNPs does not influence the survival rate of LSCC patients.

Disease Progression in Cutaneous Squamous Cell Carcinoma Patients With Satellitosis and In-transit Metastasis.

Satellitosis/in-transit metastasis (S-ITM) has prognostic value in melanoma and Merkel cell carcinoma, but is not incorporated into cutaneous squamous cell carcinoma (cSCC) staging. From our IRB-approved registry, patients with high-risk cSCC, including patients with S-ITM, were identified. Univariate (UVA) and multivariate (MVA) analyses were performed to compare disease progression (DP) and overall survival (OS). Cumulative incidence of DP and OS analyses were performed using Fine-Gray and Kaplan-Meier methods, respectively. A total of 18 S-ITM subjects were compared to 247 high risk subjects including T3N0 (n=143), N1-N3 without extranodal extension (ENE) (n=56), N1-N3 with ENE (n=26) and M1 disease (n=22). Median follow up was 16.5 months. Three-year rates of DP were 22% for T3N0, 42% for S-ITM, 48% for T4 bone invasion, 50% for N1-N3 without extranodal extension (ENE), 53% for N1-N3 with ENE, and 66% for M1. Patients with S-ITM did not experience significantly worse DP compared to those with T3N0 (HR=1.96, 95%CI=0.8-4.9; p=0.14). Cutaneous SCC patients with S-ITM experienced outcomes similar to locally advanced non-metastatic cSCC patients. Larger studies are needed to guide incorporation into staging systems.

Differentiation and TNM staging of Oral Squamous Cell Carcinoma

Head and neck carcinoma has great regional distribution in sub sites with distinct anatomical and physiological variation. Alcohol consumption, excessive smoking and hematopoetic stem cell transplantation are common risk factors for head and neck carcinoma. Alcohol consumption &amp; tobacco chewing has a strong relationship with the development of oral, larynx, pharynx cancers. A typical HNSCC has a superficial changes such as scaling, crusting, presence of cutaneous horn and ulceration. The stage of disease is apparent in the form of symptoms of head and neck carcinoma. Genetic alterations accumulation is source of initiation and development of carcinogenic cells. The development of HNSCC is based on many factors. Its underlying mechanism is based on the genetic and molecular changes along with repetitive injury to the epithelial layer by external stimuli. Different types of smoking such as Cigar, Pipe, Huqqa etc exist in sub-continent and smoke from these sources contain toxic agents like tar and carbon monoxide. Mouth cavity and lungs are the places where tar being sticky substance deposits and cause many respiratory and oral diseases.

Association between the site of occurrence and pathological TNM staging in oral squamous cell carcinoma

Oral cancer is a worldwide health problem. Risk factors for oral squamous cell carcinoma (OSCC) are tobacco, alcohol, betel nuts, viral infection and dietary habit. The site of occurence of the OSCC differs substantially between different people groups mainly because of variations in the prevalence of risk factors. The prognosis varies based on the site. pTNM is also one of the most useful tools for the prediction of prognosis. Therefore, it is of interest to correlate the pTNM staging with the site of occurrence of the lesion using 36 OSCC case reports. The results revealed 36.11% of the lesion occurred in buccal mucosa. Stage III pTNM was most prevalent in buccal mucosa and tongue and Stage IV pTNM in the retromolar trigone region by significant association with p value &lt; 0.05. Thus, we report that lesions occurring in the Retromolar region, tongue and buccal mucosa need to be given special attention, as they are associated with early metastasis and poor prognosis. Early diagnosis and appropriate treatment protocol will improve the quality of life for the patients.

Histological criteria for “intraepithelial squamous cell carcinoma” of the esophagus: continued dialogue between Ukrainian and Japanese pathologists

Patients with esophageal squamous cell carcinoma (SCC) have a poor prognosis mostly due to the late diagnosis. A morphological method is still the main diagnostic method for SCC. The aim of the study was to find out which histological criteria, namely Western or Japanese criteria, for early stage SCC are used by pathologists in Ukraine as compared with their Japanese colleagues. 14Ukrainian and 6Japanese pathologists have participated in this study. Virtual slides for research were provided by National Cancer Research Center (Tokyo, Japan) in 2018. Each of the pathologists has used these slides and presented the conclusion via the Internet. Essential diagnostic discrepancies were revealed: a number of biopsy specimens was diagnosed by Japanese pathologists as "noninvasive carcinoma", while Ukrainian pathologists classified the specimens as high-grade or low-grade dysplasia, indefinite for neoplasia, or reactive/regenerative lesions. The adoption of a unified concept of criteria for non-invasive (intraepithelial) carcinoma underlies early endoscopic/surgical treatment, which significantly increases the survival rate of patients with SCC. A solid common approach to the diagnosis between Western and Japanese pathologists, as well as endoscopists, is necessary to ensure timely treatment and increase survival rate of patients with SCC.

Geographical heterogeneity in the American Joint committee on Cancer oral cancer staging and prognostic implications.

The AJCC 8th edition (AJCC 8) has introduced depth of invasion (DOI) and extranodal extension (ENE) into staging for oral squamous cell carcinoma (OSCC). Although validations have been performed on institutional datasets have shown a good performance, particularly in early OSCC, there have been no studies on diverse patient populations that determine the impact on prognostic heterogeneity. Retrospective analysis of 4710 patients with oral squamous cell carcinoma (OSCC) treated with surgery +/- adjuvant therapy in 8 institutions in Australia, North America and Asia. With overall survival (OS) as endpoint, the prognostic performance of AJCC 7th and 8th editions were compared using Akaike Information Criterion (AIC), Bayesian Information Criteria (BIC), Harrell's concordance index (C-index). When comparing AJCC 8 to AJCC 7, the heterogeneity in prediction of OS increased for T-category and N-category while remaining unchanged for TNM staging, suggesting AJCC 8 increased complexity with no improvement in predictive value. There were significant differences in median DOI and incidence of ENE between geographical regions, resulting in dissimilar rates of stage-migration when adopting AJCC 8. In an attempt to improve prognostic performance, AJCC 8 introduced more variables; however heterogeneity in these results in significant geographical differences in model discrimination and performance. Caution should be applied as this may result in inaccurate and unreliable prognostic predictions that may impact treatment recommendations.

Expression of Cyclin D1 in oral squamous cell carcinoma and its correlation with histopathological differentiation

Cyclin D1 is a vital protein that has a widespread role in cell cycle regulations, providing control over G1 to S Phase transition and governing cell proliferation rates.Cyclin D1 overexpression has been reported in variety of tumors. Present study was carried out to the study the expression of cyclin D1 and its association with histopathological differentiation and stage of oral squamous cell carcinoma.48 formalin fixed paraffin embedded tissue blocks of biopsy specimens of oral squamous cell carcinoma were immunohistochemically evaluated for expression of cyclinD1.CyclinD1 expression was seen in 98.5% (46) cases of OSCC. It did not correlate with site and staging. CyclinD1 expression was seen in 94.6% of well differentiated tumor,100% in moderately differentiated and 100% in poorly differentiated oral squamous cell carcinoma, but it was not statistically significant(p=0.065).Relatively higher frequency of Cyclin D1 immuno-reactivity observed in patients with less differentiated tumours suggest inverse correlation of Cyclin D1 expression with histological differentiation of tumour.

Racial disparities in receipt of standard chemoradiation in anal squamous cell carcinoma, an analysis of the National Cancer Database.

BackgroundStandard treatment for locally advanced anal squamous cell carcinoma (SCC) consists of concurrent chemoradiation. We evaluated whether racial differences exist in the receipt of standard treatment and its association with survival.MethodsFrom the National Cancer Database, we identified patients diagnosed with anal SCC (Stages 2–3) between 2004 and 2015. Using logistic regression, we evaluated racial differences in the probability of receiving standard chemoradiation. We used Cox proportional hazards models to evaluate associations between race, receipt of standard therapy and survival.ResultsOur analysis included 19,835 patients. Patients receiving standard chemoradiation had better survival than patients receiving nonstandard therapy (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.61–0.68; p < 0.001). Compared to White patients, Black patients were less likely to receive standard therapy (odds ratio [OR] 0.85; 95% CI 0.76–0.96; p < 0.008). We observed no statistical difference in mortality between Black and White patients overall (HR 1.05, 95% CI 0.97–1.15; p = 0.24). However, for the subgroup of patients receiving nonstandard therapy, Black patients had an increased mortality risk compared to White patients (HR 1.17, CI 1.01–1.35; p = 0.034). We observed no survival differences in the subgroup of patients receiving standard treatment (HR 1.00, CI 0.90–1.11, p = 0.99).ConclusionStandard treatment in anal SCC is associated with better survival, but Black patients are less likely to receive standard treatment than White patients. Although Black patients had higher mortality than White patients in the subgroup of patients receiving nonstandard therapy, this difference was ameliorated in the subset receiving standard therapy.

Treatment of Early Stage Tonsil Cancer in the Age of Human Papillomavirus-Associated Malignancies.

To investigate the patterns of care and outcomes of treatment of early stage tonsil cancers, controlling for human papillomavirus (HPV) status. Historical cohort study. National Cancer Database (NCDB). Review of the NCDB between 2010 and 2017 for all T1-2N0M0 tonsillar squamous cell carcinoma (SCC). Demographics, clinical characteristics, HPV status, treatment regimens, and survival were analyzed. A total of 4720 patients were identified with early stage SCC of the tonsil. Most were tested for HPV (2759 [58.5%]). Among tested patients, 1758 (63.7%) were positive for HPV and 1001 (36.3%) were negative for HPV. HPV-positive patients had higher 3-year survival compared to HPV-negative patients (93.2% vs 77.8%, P < .001). Among HPV-positive patients, there was no significant difference in survival between treatment cohorts. However, in the HPV-negative cohort, 3-year survival was higher in both bimodality surgical-based settings (tonsillectomy + neck dissection + radiotherapy, 86.0% vs chemoradiotherapy, 69.6%, P = .01) and for all surgical-based treatments when compared to nonsurgical management (84.6% vs 69.3%, P < .001). This difference was maintained in multivariable regression controlling for age, sex, comorbidities, clinical T stage, and treatments. In a subpopulation of HPV-negative patients propensity score matched by all factors significant in multivariable analysis, 3-year survival remained higher in the surgically treated group compared to the nonsurgically treated cohort (84.9% vs 67.1%, P < .001). Surgical- or radiation-based treatment resulted in similar survival in early stage HPV-positive tonsil cancer. Surgical-based treatments were associated with longer survival in HPV-negative cancers. These findings should be further investigated in a randomized prospective trial.

Metformin use and lung cancer survival: a population-based study in Norway

BackgroundWe assessed associations between metformin use and survival in a nationwide Norwegian cohort of lung cancer (LC) patients.MethodsThe study linked 22,324 LC patients from the Cancer Registry of Norway diagnosed 2005–2014 with the Norwegian Prescription Database. We estimated associations of pre- and post-diagnostic metformin use with overall survival (OS) and LC-specific survival (LCSS) using multivariable time-fixed and time-dependent Cox regression.ResultsPre-diagnostic metformin use was not associated with improved survival in all patients. Nevertheless, pre-diagnostic metformin use was associated with better LCSS in squamous cell carcinoma (SCC) patients (hazard ratio (HR) = 0.79; 95% confidence interval (CI) 0.62–0.99) and in patients with regional stage SCC (HR = 0.67; 95%CI 0.47–0.95). Post-diagnostic metformin use was associated with improved LCSS in all patients (HR = 0.83; 95%CI 0.73–0.95), in patients with SCC (HR = 0.75; 95%CI 0.57–0.98), regional stage LC (HR = 0.74; 95%CI 0.59–0.94), and regional stage SCC (HR = 0.57; 95%CI 0.38–0.86). OS showed similar results. Analyses of cumulative use showed a dose-response relationship in all patients, patients with adenocarcinoma and SCC, and with regional and metastatic LC.ConclusionsMetformin use was associated with improved survival, especially LCSS in patients with regional stage SCC. Further prospective studies are required to clarify the role of metformin in LC treatment.