Favorable Disease-specific Survival Research Articles

TET1 is a Diagnostic and Prognostic Biomarker Associated with Immune Infiltration in Papillary Thyroid Cancer.

To investigate the function of ten-eleven translocation 1 (TET1) and its underlying mechanism in papillary thyroid cancer (PTC). Using the RNA-Seq data based on GDC TCGA, we analyzed the gene expression pattern of TET1 in PTC. Immunohistochemistry was carried out to assess the TET1 protein level. Then, its diagnostic and prognostic functions were determined by various bioinformatics approaches. Enrichment analysis was performed to explore the potential pathways in which TET1 is mainly involved. Finally, the immune cell infiltration analysis was conducted and the association of TET1 mRNA expression with the expression levels of immune checkpoints, tumor mutation burden (TMB) score, microsatellite instability (MSI) score, and cancer stem cells (CSC) score was examined. TET1 expression was lower in PTC tissues compared with that in normal tissues (P < 0.01). Besides, TET1 had a certain value in diagnosing PTC, and low-TET1 mRNA expression led to favorable disease-specific survival (DSS) (P < 0.01). The enrichment analysis revealed autoimmune thyroid disease and cytokine-cytokine receptor interaction were the consistent pathways in which TET1 participated. TET1 was negatively correlated with the Stromal score and Immune score. The different proportions of immune cell subtypes were observed between high- and low-TET1 expression groups. Interestingly, TET1 mRNA expression was inversely related to the expression levels of immune checkpoints, and TMB, MSI, and CSC scores. TET1 might be a robust diagnostic and prognostic biomarker for PTC. TET1 affected the DSS of PTC patients possibly through the regulation of immune-related pathways and tumor immunity.

Abstract 5564: SerpinE2: A potential biomarker for urological cancers

Abstract SerpinE2, also known as protease nexin-1, is an extracellular serine protease inhibitor modulating the activity of serine proteases such as thrombin, plasmin, urokinase-type plasminogen activator and trypsin. Dysregulation between extracellular serine proteases and their cognate inhibitors has been implicated in malignant progression, making serpins promising biomarkers for tumor progression and prognosis. SerpinE2 is upregulated in many cancers and promotes tumor invasion and metastasis. In this study, we analyzed serpinE2 expression by immunohistochemistry on tissue microarrays comprising of samples from prostate, bladder and kidney cancers. The studied samples were clinically hard-to-risk stratify and thus relevant for biomarker studies. We aimed to study the association of serpinE2 expression with survival and clinicopathological features in all three cancers, and evaluate its potential as an immunohistochemical biomarker. In the case of bladder cancer, association of serpinE2 expression with response to neoadjuvant chemotherapy was also assessed. We found that although the strong expression of serpinE2 was related to more aggressive prostate cancers (p = 0.017) and high grade bladder cancers (p = 0.034), it was not associated with relapse, treatment response or survival of prostate and bladder cancer patients. In renal cancer, on the contrary, serpinE2 expression was significantly lower in patients with tumor relapse (p = 0.048) and high expression predicted favorable disease-specific survival (p = 0.013). Our findings help understanding the functional role of serpinE2 in cancer progression and guide the prognostic biomarker research of serpinE2, particularly for prediction of renal cancer-specific survival. Citation Format: Ruusu-Maaria Kovanen, Netta Koskinen, Timo-Pekka Lehto, Antti Rannikko, Tuomas Mirtti, Hannu Koistinen. SerpinE2: A potential biomarker for urological cancers. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5564.

Prognostic impact of variant histologies in urothelial bladder cancer treated with radical cystectomy.

To evaluate variant histologies (VHs) for disease-specific survival (DSS) in patients with invasive urothelial bladder cancer (BCa) undergoing radical cystectomy (RC). We analysed a multi-institutional cohort of 1082 patients treated with upfront RC for cT1-4aN0M0 urothelial BCa at eight centres. Univariable and multivariable Cox' regression analyses were used to assess the effect of different VHs on DSS in overall cohort and three stage-based analyses. The stages were defined as 'organ-confined' (≤pT2N0), 'locally advanced' (pT3-4N0) and 'node-positive' (pTanyN1-3). Overall, 784 patients (72.5%) had pure urothelial carcinoma (UC), while the remaining 298 (27.5%) harboured a VH. Squamous differentiation was the most common VH, observed in 166 patients (15.3%), followed by micropapillary (40 patients [3.7%]), sarcomatoid (29 patients [2.7%]), glandular (18 patients [1.7%]), lymphoepithelioma-like (14 patients [1.3%]), small-cell (13 patients [1.2%]), clear-cell (eight patients [0.7%]), nested (seven patients [0.6%]) and plasmacytoid VH (three patients [0.3%]). The median follow-up was 2.3 years. Overall, 534 (49.4%) disease-related deaths occurred. In uni- and multivariable analyses, plasmacytoid and small-cell VHs were associated with worse DSS in the overall cohort (both P= 0.04). In univariable analyses, sarcomatoid VH was significantly associated with worse DSS, while lymphoepithelioma-like VH had favourable DSS compared to pure UC. Clear-cell (P= 0.015) and small-cell (P= 0.011) VH were associated with worse DSS in the organ-confined and node-positive cohorts, respectively. More than 25% of patients harboured a VH at time of RC. Compared to pure UC, clear-cell, plasmacytoid, small-cell and sarcomatoid VHs were associated with worse DSS, while lymphoepithelioma-like VH was characterized by a DSS benefit. Accurate pathological diagnosis of VHs may ensure tailored counselling to identify patients who require more intensive management.

Prognostic Impact of Hepatic Steatosis Evaluated by CT on Immunotherapy for Gastric Cancer: Associations with Sarcopenia, Systemic Inflammation, and Hormones

Introduction: Immune checkpoint inhibitors (ICIs) are expected to improve the prognosis of gastric cancer (GC). Also, hepatic steatosis has been reported to be associated with cancer cachexia and is expected to be a cancer biomarker. The purpose of this study was to evaluate prognostic impact of hepatic steatosis in ICI therapy for GC. Methods: Unresectable or recurrent GC treated with ICIs was investigated. Using unenhanced CT, the liver-to-spleen CT attenuation ratio (LSR) was calculated as a parameter of hepatic steatosis. LSR was compared with the presence of sarcopenia and inflammatory markers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). These parameters were also compared with disease-specific survival (DSS) and progression-free survival (PFS). Associations of LSR with insulin-like growth factor 1 (IGF-1) and growth hormone were also evaluated. Results: A total of 70 patients were investigated. LSR of sarcopenia patients was significantly lower than that of non-sarcopenic ones (p = 0.02). LSR showed significant negative correlations with NLR, PLR, and MLR (p = 0.003, 0.03, 0.01, respectively). Lower LSR was significantly associated with a higher level of serum IGF-1 (p = 0.03). In univariate analysis, LSR was significantly correlated with DSS and PFS (both p < 0.0001), and multivariate analysis demonstrated that LSR was the independent prognostic factor for both DSS and PFS (both p = 0.01). ROC analysis demonstrated that LSR >1.263 was a good predictive marker for favorable DSS (>5.3 months) with an AUC of 0.80. Conclusion: Hepatic steatosis can be a promising prognostic biomarker for ICI therapy of GC, associated with sarcopenia and the elevation of inflammatory markers. Our data suggested that GC with steatohepatitis might be less responsive to ICI therapy.

T cell-inflamed gene expression profile is associated with favorable disease-specific survival in non-hypermutated microsatellite-stable colorectal cancer patients.

The anti-tumor immune response plays a key role in colorectal cancer (CRC) progression and survival. The T cell-inflamed gene expression profile (GEP) is a biomarker predicting response to checkpoint inhibitor immunotherapy across immunogenic cancer types, but the prognostic value in CRC is unknown. We evaluated associations with disease-specific survival, somatic mutations, and examined its differentially expressed genes and pathways among 84 sporadic CRC patients from the Seattle Colon Cancer Family Registry. Gene expression profiling was performed using Nanostring's nCounter PanCancer IO 360 panel. Somatic mutations were identified by a targeted DNA sequencing panel. The T cell-inflamed GEP was positively associated with tumor mutation burden and microsatellite instability high (MSI-H). Higher T cell-inflamed GEP had favorable CRC-specific survival (hazard ratio [HR] per standard deviation unit=0.50, p=0.004) regardless of hypermutation or MSI status. Analysis of recurrently mutated genes having at least 10 mutation carriers, suggested that the T cell-inflamed GEP is positively associated with RYR1, and negatively associated with APC. However, these associations were attenuated after adjusting for hypermutation or MSI status. We also found that expression of genes RPL23, EPCAM, AREG and ITGA6, and the Wnt signaling pathway was negatively associated with the T cell-inflamed GEP, which might indicate immune-inhibitory mechanisms. Our results show that the T cell-inflamed GEP is a prognostic biomarker in non-hypermutated microsatellite-stable CRC. This also suggests that patient stratification for immunotherapy within this CRC subgroup should be explored further. Moreover, reported immune-inhibitory gene expression signals may suggest targets for therapeutic combination with immunotherapy.

High expression of miR-17-5p and miR-20a-5p predicts favorable disease-specific survival in stage I-III colon cancer

In many types of cancer, microRNAs (miRs) are aberrantly expressed. The aim of this study was to explore the prognostic impact of miR-17-5p and miR-20a-5p in colon cancer. Tumor tissue from 452 stage I-III colon cancer patients was retrospectively collected and tissue microarrays constructed. miR-17-5p and miR-20a-5p expression was evaluated by in situ hybridization and analyzed using digital pathology. Cell line experiments, using HT-29 and CACO-2, were performed to assess the effect of miR-17-5p and miR-20a-5p over expression on viability, invasion and migration. In multivariate analyses, high miR-17-5p expression in tumor (HR = 0.43, CI 0.26–0.71, p < 0.001) and high expression of miR-20a-5p in tumor (HR = 0.60, CI 0.37–0.97, p = 0.037) and stroma (HR = 0.63, CI 0.42–0.95, p = 0.027) remained independent predictors of improved disease-specific survival. In cell lines, over expression of both miRs resulted in mitigated migration without any significant effect on viability or invasion. In conclusion, in stage I-III colon cancer, high expression of both miR-17-5p and miR-20a-5p are independent predictors of favorable prognosis.

Elective neck dissection improves the survival of patients with T2N0M0 oral squamous cell carcinoma: a study of the SEER database

BackgroundTreatment of clinical N0 neck tumours is controversial in early-stage oral squamous cell carcinoma (OSCC), possibly because T1N0M0 and T2N0M0 merge together at early stages. The purposes of this study were to compare survival outcomes only for T2N0M0 cases based upon treatment elective neck dissection versus neck observation.MethodsT2N0M0 OSCC cases were identified in the Surveillance, Epidemiology, and End Results database of the United States National Cancer Institute between 2004 and 2015. Survival curves for different variable values were generated using Kaplan-Meier estimates and compared using the log-rank test. Variables that achieved significance at P < 0.05 were entered into multivariable analyses via the Cox proportional hazards multivariate regression.ResultsA total of 2857 patients were selected, and 2313 cases were available for disease specific survival (DSS). The 5-year and 10-year overall survival (OS) were 66.7 and 46% for patients receiving elective neck dissection (END), respectively, and 56.4 and 37.2% for patients with neck observation (P < 0.0001). The 5-year and 10-year DSS were 73.6 and 64% for the END group, respectively, versus 64.5 and 54.5% for the neck observation group (P < 0.0001). More importantly, performing END was independently associated with favourable DSS and OS for patients with T2N0M0 OSCC [hazard ratio (HR) = 0.769, P = 0.0069 for DSS; HR = 0.829, P = 0.0031 for OS, neck observation group as reference] according to multivariate survival analysis.ConclusionEND is recommended for T2N0M0 OSCC cases and it is associated with improved DSS and OS.

Basaloid squamous cell carcinoma of the hypopharynx: an analysis of 213 cases.

Basaloid squamous cell carcinoma (BSCC) is a rare aggressive variant of squamous cell carcinoma (SCC) with a poor prognosis. No large series of exclusively hypopharyngeal BSCC patients have been previously reported. Therefore, this retrospective population-based study aims to explain the patient demographics, clinicopathologic characteristics, incidence, and survival outcomes of hypopharyngeal BSCC and how it relates to conventional-type SCC. The National Cancer Institute's Surveillance, Epidemiology, and End Results database registry was queried for patients diagnosed with hypopharyngeal BSCC and conventional-type SCC between 2001 and 2016. The incidence of hypopharyngeal BSCC from 2001 to 2016 was 0.0161 per 100,000 individuals. The BSCC group comprised 213 patients, and the SCC group 7958 patients. The majority of BSCCs were considered high grade (Grade III/IV, 89.58%). Most BSCC patients were diagnosed at an advanced stage (American Joint Committee on Cancer [AJCC] stage IV, 65.38%). The 1-, 5-, and 10-year disease-specific survival (DSS) rates for hypopharyngeal BSCC were 84.10%, 57.40%, and 46.20%, respectively. Multivariate analysis, after adjustment for sex, age, race, tumor location, grade, and AJCC stage, showed that patients with BSCC had significantly better DSS than those with conventional-type SCC. Surgery with radiation contributed to a favorable DSS for BSCC patients in comparison with other treatments. This analysis of the largest hypopharyngeal BSCC series indicates a better prognosis for this pathologic type compared with conventional-type hypopharyngeal SCC. Multimodality treatment with surgery and radiation may result in a favorable prognosis for hypopharyngeal BSCC patients.

Integrated molecular characterisation of endometrioid ovarian carcinoma identifies opportunities for stratification

Endometrioid ovarian carcinoma (EnOC) is an under-investigated ovarian cancer type. Recent studies have described disease subtypes defined by genomics and hormone receptor expression patterns; here, we determine the relationship between these subtyping layers to define the molecular landscape of EnOC with high granularity and identify therapeutic vulnerabilities in high-risk cases. Whole exome sequencing data were integrated with progesterone and oestrogen receptor (PR and ER) expression-defined subtypes in 90 EnOC cases following robust pathological assessment, revealing dominant clinical and molecular features in the resulting integrated subtypes. We demonstrate significant correlation between subtyping approaches: PR-high (PR + /ER + , PR + /ER−) cases were predominantly CTNNB1-mutant (73.2% vs 18.4%, P < 0.001), while PR-low (PR−/ER + , PR−/ER−) cases displayed higher TP53 mutation frequency (38.8% vs 7.3%, P = 0.001), greater genomic complexity (P = 0.007) and more frequent copy number alterations (P = 0.001). PR-high EnOC patients experience favourable disease-specific survival independent of clinicopathological and genomic features (HR = 0.16, 95% CI 0.04–0.71). TP53 mutation further delineates the outcome of patients with PR-low tumours (HR = 2.56, 95% CI 1.14–5.75). A simple, routinely applicable, classification algorithm utilising immunohistochemistry for PR and p53 recapitulated these subtypes and their survival profiles. The genomic profile of high-risk EnOC subtypes suggests that inhibitors of the MAPK and PI3K-AKT pathways, alongside PARP inhibitors, represent promising candidate agents for improving patient survival. Patients with PR-low TP53-mutant EnOC have the greatest unmet clinical need, while PR-high tumours—which are typically CTNNB1-mutant and TP53 wild-type—experience excellent survival and may represent candidates for trials investigating de-escalation of adjuvant chemotherapy to agents such as endocrine therapy.

Prognostic value of aldo-keto reductase family 1 member B10 (AKR1B10) in digestive system cancers: A meta-analysis.

Background:Numbers of studies have reported that the expression of aldo-keto reductase family 1 member B10 (AKR1B10) is abnormal in digestive system cancers, and could be used as a prognostic biomarker. However, the results are argued. Therefore, we conduct a meta-analysis to comprehensively evaluate the prognostic value of high AKR1B10 expression for overall survival (OS), disease specific survival (DSS), and disease-free survival/recurrence-free survival (DFS/PFS) in digestive system cancers.Methods:Hazard ratios (HRs) with its 95% confidence intervals (CIs) were calculated to assess the prognostic value of AKR1B10 by using the random effects model. The STATA version 12.0 software were used to perform all the analyses.Results:Eleven articles including 1428 patients involved in this meta-analysis. The pooled analysis suggested that high AKR1B10 expression was not associated with OS (HR: 1.18; 95% CI: 0.69–2.00) and DFS/PFS (HR: 1.08, 95% CI: 0.67–1.76) in digestive system cancers. However, Further analysis revealed that high AKR1B10 expression indicated poor OS in oral squamous cell carcinomas (OSCC) (HR: 2.92, 95% CI: 1.86–4.58) and favorable DSS in hepatocellular carcinoma (HCC) (HR: 0.71, 95% CI: 0.52–0.97).Conclusions:The prognostic value of high AKR1B10 expression varied in different types of digestive system cancers. Further studies exploring the prognostic role of AKR1B10 in digestive system cancers are needed.

Effect of age and gender in non-smokers with oral squamous cell carcinoma: Multi-institutional study

BackgroundIn developing countries, oral squamous cell carcinoma (OSCC) is predominantly a cancer affecting older males who smoke tobacco. In countries with effective public health strategies, smoking rates are declining rapidly. It is not clear if patients who develop OSCC without these traditional risk factors represent a clinically distinct cohort with different prognosis. A recent analysis found that elderly non-smoking females with OSCC had significantly worse prognosis, concluding that this was a distinct patient population with poorer survival. The primary aim of this study was to determine the effect of gender and age on prognosis in OSCC, and the interaction between these two variables. MethodsMultinational multi-institutional data were collected from six sites. The primary outcome of interest was disease specific survival (DSS). Time to local, regional, and distant recurrence were investigated as secondary outcomes. Results3379 patients with OSCC were included. Males had significantly worse DSS compared to females (HR 1.24, 95% CI 1.08–1.43, p = 0.003). Females <70 years of age had significantly better DSS compared to females ≥70 years of age (HR 0.69, 95% CI 0.51–0.94, p < 0.001) but elderly females had similar DSS to males, regardless of age. When age was divided into three groups, the middle-aged group (45–69 years) had a significantly better DSS compared to elderly patients (HR 0.87, 95%CI 0.78–0.96, p < 0.001), however younger patients had similar DSS to elderly patients. When the effect of age (young v middle v elderly) was compared in each gender, young and middle-aged females had the most favourable DSS (log-rank p < 0.001). Middle-aged females who smoked had a 10% survival advantage compared to middle-aged males that smoked at five years. ConclusionsAge, gender, tumour subsite, and smoking status are important drivers of survival in OSCC. However, gender appears to be the most important predictor with young and middle-aged females having the most favourable prognosis.

Vacuolar Membrane ATPase Activity 21 Predicts a Favorable Outcome and Acts as a Suppressor in Colorectal Cancer.

Extracellular and/or intracellular manipulation of pH in tumor may have noticeable potential in cancer treatment. Although the assembly factor genes of V0 domain of the V-ATPase complex are required for intracellular pH homeostasis, their significance in colorectal cancer (CRC) remains largely unknown. Here, we used bioinformatics to identify the candidates from known assembly factor genes of the V0 domain, which were further evaluated by immunohistochemistry (IHC) in CRC and adjacent normal specimens from 661 patients. Univariate and multivariate Cox analyses were used to evaluate factors contributing to prognosis. The effects of variations in the expression of VMA21 on tumor growth were assessed in vitro and in vivo. Of five known assembly factors, only VMA21 showed differential expression between CRC and adjacent normal tissues at both mRNA and protein levels. Patients with high VMA21 expression had higher differentiation grade and longer disease-specific survival (DSS) at stages I–III disease. High VMA21 expression in tumors was also an independent predictor of DSS (hazard ratio, 0.345; 95% confidence interval, 0.123–0.976), with covariates included TNM stage and differentiation grade. VMA21 overexpression decreased CRC growth, whereas VMA21 knockdown increased CRC growth in vitro and in vivo. VMA21 expression suppresses CRC growth and predicts a favorable DSS in patients with stage I-III disease.

A population-based analysis of adenosquamous carcinoma of the salivary gland.

Adenosquamous carcinoma (ASC) of the salivary gland is a rare malignancy, and the characteristics and prognosis of this disease remain unclear. This study aimed to assess the clinicopathological characteristics of this rare disease and further determine the potential prognostic factors that affect its outcome. Data of patients with ASC of the salivary gland were extracted retrospectively from the Surveillance, Epidemiology, and End Results (SEER) database between 1973 and 2016. The clinicopathological characteristics of these patients were assessed, and prognostic factors were further determined using Cox regression analysis. A total of 106 patients with ASC of the salivary gland were identified. The mean age at diagnosis was 66.1±14.9 years, with a male-to-female ratio of 1.47. The parotid gland was the most common primary site (N=91; 85.8%). The 1-, 2-, and 5-year overall survival (OS) rates were 71.5%, 55.0%, 41.5%, respectively. The 1-, 2-, and 5-year disease-specific survival (DSS) rates were 80.8%, 72.2%, and 59.2%, respectively. The OS and DSS shortened with increasing tumor stage, regardless of the American Joint Committee on Cancer tumor-node-metastasis stage or SEER historic stage. Surgery was the main treatment option to improve survival, and post-operative radiotherapy could also prolong OS and DSS (both P<0.01). A multivariate Cox regression analysis demonstrated that distant metastases and the use of surgery or radiation were independent prognostic factors for a favorable OS among patients with ASC of the salivary gland, and early stage (T1/T2) and the use of surgery were independent prognostic factors for favorable DSS among the patients with ASC of the salivary gland. This is the largest case series on ASC of the salivary gland. Advanced T stage, distant metastases, and the use of surgery and radiation were associated with OS or DSS of this disease.

Abstract 4161: Integrated analysis of whole exome sequencing and hormone receptor expression data in endometrioid ovarian cancer

Abstract Endometrioid ovarian carcinomas (EnOCs) account for 10% of OC diagnoses, representing distinct biological and clinical entities compared to other OC subtypes. We recently reported two molecular subgrouping studies using &amp;gt;100 WT1-negative EnOCs: the first identified molecular subgroups of disease by unsupervised analysis of hormone receptor expression patterns, reporting favorable disease-specific survival (DSS) in the PR-high subgroups (PR+/ER+, PR+/ER- vs PR-/ER+, PR-/ER-). The latter study performed whole exome sequencing, identifying genomic events associated with differential DSS, including TP53 mutation (TP53m) and CTNNB1m. Here, we perform integrated analysis of these data to investigate the overlap between these molecular subgrouping layers. The PR-high subgroups demonstrated low TP53m rate (5% vs 26%, P=0.035) and frequent CTNNB1m (75% vs 26%, P&amp;lt;0.001), with the highest CTNNB1m rate in the PR+/ER+ subgroup (84%, 21/25). Accordingly, TP53m cases demonstrated significantly lower median histoscore (mHS) for PR (3 vs 203, P=0.028) and a trend for lower ER (mHS 66 vs 160, P=0.056), while cases with CTNNB1m demonstrated significantly higher PR and ER expression (mHS 258 vs 40, P&amp;lt;0.001 and 181 vs 75, P=0.002). There was no significant difference in tumor mutational burden, microsatellite instability or tumor heterogeneity as defined by Mutant Allele Tumour Heterogeneity (MATH) score between the hormone-receptor-based subgroups. These groups also demonstrated no significant difference in mutation rate of mismatch repair protein-encoding genes. Multivariable analysis identified only FIGO stage at diagnosis (P=0.002), optimal surgical debulking (P=0.035) and hormone receptor subgroup (P=0.004) as independently associated with DSS. TP53m and CTNNB1m were not independently associated with DSS (P=0.187 and P=0.166), though CTNNB1m demonstrated a trend for association in a corresponding model for relapse-free survival (RFS) (HR=0.26, P=0.064). Within PR-high cases, specific genomic events were not associated with significantly differential survival. Conversely, TP53m was associated with inferior outcome specifically in PR-low cases (P=0.010 for RFS; P=0.066 for DSS). Collectively, these data represent the first depiction of the overlay and interplay between recently identified EnOC subgroups defined by WES and hormone receptor expression patterns. They demonstrate that PR-high cases frequently harbor CTNNB1m, while TP53m is rare in this context. Moreover, they suggest that PR-high cases experience favorable outcome irrespective of genomic profile, while TP53m represents an important marker of prognosis in PR-low EnOC. Moreover, given the high expression of ER and PR in the CTNNB1m population, assessment of the potential efficacy of endocrine therapy in this population may now warrant investigation. Citation Format: Robert L. Hollis, John Thomson, Barbara Stanley, Alison M. Meynert, Michael Churchman, Tzyvia Rye, C. Simon Herrington, Charlie Gourley. Integrated analysis of whole exome sequencing and hormone receptor expression data in endometrioid ovarian cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4161.

Squamous cell carcinoma associated with inverted papilloma: Recurrence and prognostic factors

The purpose of the present study was to review the recurrence and prognostic factors of squamous cell carcinoma (SCC) associated with inverted papilloma (IP). A retrospective chart review was conducted on 21 patients with SCC associated with IP, in the nasal cavity and paranasal sinuses, between March 2007 to March 2017. All patients underwent surgical treatment: Surgery prior to or following adjuvant therapy was performed in 17 patients (81.0%). During a mean follow-up time of 47.4 months (range, 3-123 months), 9 patients (42.9%) experienced local recurrence, and the risk factors of T4 stage and invasive orbital cavity had a significant influence on recurrence. The 1-, 3-, and 5-year overall survival rates were 90.5, 75.4 and 68.5%, and the 1-, 3-, and 5-year disease-specific survival (DSS) rates were 90.5, 80.4 and 80.4%, respectively. The prognosis of patients with stage T4 was not satisfactory compared with those with stage T3 or less, and a positive surgical margin was also significantly associated with poor survival. Overall, SCC associated with IP has a favorable DSS, early diagnosis and complete resection of lesions is required for a good prognosis. Furthermore, aggressive surgical approaches combined with postoperative adjuvant therapy seem to be effective in tumors at stage T4.

Prognostic implications of human papillomavirus type 16 status in non-oropharyngeal head and neck cancer: a propensity score matching analysis.

The purpose of this study was to investigate the association between HPV 16 status and survival outcomes in patients with non-oropharyngeal squamous carcinoma (non-OPSCC). Patients with non-OPSCC diagnosed between 2006 and 2016 were included in this study. The presence of HPV 16 DNA was confirmed by quantitative real-time polymerase chain reaction. Survival analysis was performed using Kaplan-Meier estimates, the Cox proportional hazards model, and propensity score matching (PSM). Overall, 1,539 patients with adequate specimens were identified, of whom 131 (8.51%) were positive for HPV 16. Compared to HPV 16-negative patients, the adjusted hazard ratios (aHR) for HPV 16-positive non-OPSCC patients were 0.77 and 0.81 for disease-specific survival (DSS) and overall survival (OS), respectively. Additionally, the larynx was the only subsite in which DSS was significantly improved. After PSM, cohorts consisted of 129 patients in the HPV 16-positive group and 129 in the HPV 16-negative group. HPV 16-positive non-OPSCC patients had favorable survival outcomes, however, these outcomes were not significantly different compared to HPV 16-negative patients. Stratified analysis performed according to primary site showed that only in the larynx was HPV 16-positive status a significant factor for predicting favorable DSS. Our findings indicate that HPV 16-positive non-OPSCC patients did not have significantly better survival outcomes compared to HPV 16-negative patients.

Desmoplastic melanoma: Demographic and clinicopathological features and disease-specific prognostic factors.

Desmoplastic melanoma (DM) is a rare morphological subtype of melanoma that remains uncharacterized. The aim of the present study was to investigate the incidence of DM, its general demographics, clinicopathological features and disease-specific prognostic factors. DM cases were sampled from the Surveillance, Epidemiology and End Results (SEER) program from between 1973 and 2017. A total of 3,657 cases (median age, 68 years) were identified. The results indicated that DM primarily occurred in Caucasian subjects, with a male-to-female ratio of 2:1. Statistically significant overall survival (OS) and disease-specific survival (DSS) rate differences were identified according to sex, age, treatment, T stage, N stage and SEER historic tumor stage (P<0.05). In multivariate Cox regression analysis, age >68 years, male sex, American Joint Committee on Cancer (AJCC) stage II and III, and SEER historic tumor stage of the regional tumor were all factors associated with poorer OS and DSS rates. The findings also revealed that surgical treatment was associated with favorable DSS and OS rates. In conclusion, DM occurred primarily in Caucasian subjects of 60–80 years of age, with predominance in males. Furthermore, age, sex, AJCC stage, SEER historic tumor stage and surgical treatment were identified as independent prognostic factors of DM in terms of DSS and OS.

Stage I non-Hodgkin lymphoma: no plateau in disease-specific survival ?

Stage I non-Hodgkin lymphoma (NHL) is rare; prognostic impact of different histologic subtypes and treatment modality is still unclear. We used the Surveillance, Epidemiology and End Results (SEER) database to evaluate survival outcomes among adult patients (age ≥ 18years, N = 58,230) diagnosed with stage I NHL of various histologic subtypes between 1998 and 2014. Five-year disease-specific survival of patients with stage I diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), Burkitt lymphoma (BL), mantle cell lymphoma (MCL), and peripheral T cell lymphoma (PTCL) was 82%, 92%, 95%, 89%, 78%, 77%, and 77%, respectively. The median disease-specific survival was not reached in all histologic subtypes analyzed; however, there does not appear to be a plateau in disease-specific survival of patients with stage I NHL irrespective of subtypes. Although lymphoma was the most common cause of death (40.7%), death from other cancer (17.4%) and cardiovascular disease (13.6%) were also frequent. Chemotherapy appeared favorably associated with OS in patients with DLBCL, BL, and MCL while patients with FL, MZL, SLL, and PTCL who require chemotherapy for initial treatment showed shorter OS. Patients with stage I NHL have favorable disease-specific survival; however, no plateau was seen regardless of histologic subtypes thus suggesting that patients may need attention and follow-up even in aggressive lymphomas after 5years of remission.

Prognostic Significance of HPV and p16 Status in Men Diagnosed with Penile Cancer: A Systematic Review and Meta-analysis.

It has been shown that human papillomavirus (HPV) and p16 status has prognostic value in some HPV-associated cancers. However, studies examining survival in men with penile cancer according to HPV or p16 status are often inconclusive, mainly because of small study populations. The aim of this systematic review and meta-analysis was to examine the association between HPV DNA and p16 status and survival in men diagnosed with penile cancer. Multiple electronic databases were searched. Twenty studies were ultimately included and study-specific and pooled HRs of overall survival and disease-specific survival (DSS) were calculated using a fixed effects model. In the analysis of DSS, we included 649 men with penile cancer tested for HPV (27% were HPV-positive) and 404 men tested for p16 expression (47% were p16-positive). The pooled HRHPV of DSS was 0.61 [95% confidence interval (CI), 0.38-0.98], and the pooled HRp16 of DSS was 0.45 (95% CI, 0.30-0.69). In conclusion, men with HPV or p16-positive penile cancer have a significantly more favorable DSS compared with men with HPV or p16-negative penile cancer. These findings point to the possible clinical value of HPV and p16 testing when planning the most optimal management and follow-up strategy. Cancer Epidemiol Biomarkers Prev; 27(10); 1123-32. ©2018 AACR.

LAG-3 in Non–Small-cell Lung Cancer: Expression in Primary Tumors and Metastatic Lymph Nodes Is Associated With Improved Survival

BackgroundLymphocyte activation gene-3 (LAG-3) is an immune checkpoint receptor and a putative therapeutic target in non–small-cell lung cancer (NSCLC). We explored the prognostic effect of LAG-3+ tumor-infiltrating lymphocytes (TILs) in primary tumors and metastatic lymph nodes in NSCLC and its potential for inclusion in an immunoscore, supplementing the TNM classification. Materials and MethodsPrimary tumor tissue from 553 stage I-IIIB NSCLC patients and 143 corresponding metastatic lymph nodes were collected. The expression of LAG-3 was evaluated by immunohistochemistry on tissue microarrays. ResultsOn univariate analysis, LAG-3+ TILs in the intraepithelial and stromal compartments of primary tumors and in the intraepithelial and extraepithelial compartments of metastatic lymph nodes were associated with improved disease-specific survival (DSS). On multivariate analysis, stromal LAG-3+ TILs were a significant independent predictor of improved DSS (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.43-0.82; P = .002). Stromal LAG-3+ TILs did not have prognostic impact across all pathologic stages. In the metastatic lymph nodes, intraepithelial (HR, 0.61; 95% CI, 0.38-0.99; P = .049) and extraepithelial (HR, 0.54; 95% CI, 0.29-0.70; P < .001) LAG-3+ TILs were independently associated with favorable DSS. ConclusionLAG-3+ TILs are an independent positive prognostic factor in stage I-IIIB NSCLC. LAG-3 in metastatic lymph nodes is a candidate marker for an immunoscore in NSCLC.