Nephron-sparing Management of Upper Tract Urothelial Carcinoma

Upper tract urothelial carcinoma (UTUC) is a relatively rare tumor, but is characterized by high rates of recurrence, morbidity, and mortality. Choice of treatment modality is generally influenced by lesion size, grade, and focality. Radical nephroureterectomy with bladder cuff excision is the gold-standard management of UTUC, although an organ-sparing approach may be beneficial in selected patients. Conservative endoscopic management of UTUC in appropriate patients has a favorable impact on quality of life and health care costs when compared with patients who progress to dialysis-dependent renal failure. Careful ureteroscopic surveillance following endoscopic management of UTUC is essential.Key words: Upper tract urothelial carcinoma, Tumor grade, Nephron-sparing endoscopic treatment, Topical adjuvant chemo-immunotherapy, Oncologic outcomesUpper tract urothelial carcinoma (UTUC) accounts for < 5% of all cases of urothelial neoplasia, but is a very morbid disease, with recurrence rates up to 90%^1–9 and 5-year survival rates ranging from 30% to 60%.¹⁰ Radical nephroureterectomy (NU) with bladder-cuff excision has been the traditional treatment for UTUC because of its high rate of recurrence. However, given the morbidity of nephrectomy and the risk of developing chronic kidney disease (CKD) or dialysis-dependent renal failure, as well as the risk of contralateral tumors,^11–14 a nephron-sparing approach may be preferable in selected patients.     

Prognostic Significance of Preoperative Albumin-Globulin Ratio in Patients with Upper Tract Urothelial Carcinoma

Background

Preoperative albumin-globulin ratio (AGR) reflects both malnutrition and systemic inflammation in cancer patients. In particular, systemic inflammation has been reported to contribute to tumor progression and poor oncological outcome in various malignancies. However, the prognostic value of preoperative AGR in upper tract urothelial carcinoma (UTUC) has not been examined.

Methods

We retrospectively reviewed medical data of 187 operable UTUC patients in a Chinese cohort with a high incidence of chronic kidney disease (CKD). AGR was calculated as [AGR = albumin/(serum total protein—albumin)]. The associations of preoperative AGR with clinicopathologic characteristics and prognosis were assessed. Multivariate analyses using Cox regression models were performed to determine the independent prognostic factors.

Results

The median (IQR) preoperative AGR was 1.50 (1.30–1.70), and the optimal cutoff value was determined to be 1.45 according to the receiver operating curve analysis. Low AGR was significantly associated with female gender, high CKD stage and tumor grade (P < 0.05). Eighty-three patients died before the follow-up endpoint. Kaplan-Meier analysis showed that an AGR < 1.45 predicted significantly poorer overall and cancer-specific survivals compared to an AGR ≥ 1.45 (P < 0.001 and P = 0.008, respectively). Multivariate analyses showed that an AGR < 1.45 was an independent risk factor for poorer overall and cancer-specific survivals (P = 0.002 and P = 0.015, respectively).

Conclusions

Preoperative AGR can act as an effective biomarker with easy accessibility for evaluating the prognosis of patients with UTUC. AGR should be applied in UTUC patients for risk stratification and determination of optimal therapeutic regimens.     

NFATc1 Expression as a Prognosticator in Urothelial Carcinoma of the Upper Urinary Tract

We recently found that NFATc1, a member of the NFAT family and a key regulator of the immune response, could induce bladder carcinogenesis and cancer progression. In this study, we immunohistochemically stained for NFATc1 in upper urinary tract urothelial carcinoma (UUTUC) specimens and paired nonneoplastic urothelial tissues. NFATc1 was positive in 51 [52%; 40 (40%) weak (1+), 9 (9%) moderate (2+), and 2 (2%) strong (3+)] of 99 UUTUCs, which was significantly higher than in benign urothelium [30 (36%) of 83; 28 (34%) weak and 2 (2%) moderate] (0 vs 1+/2+/3+, P = .038; 0/1+ vs 2+/3+, P = .023). There were no significant associations between NFATc1 expression pattern and tumor grade or pT stage. However, the positive rates of NFATc1 expression tended to be higher in renal pelvic tumors (60%) than in ureteral tumors (42%; P = .080) as well as in pN+ tumors (75%) than in pN0 tumors (49%; P = .089). Kaplan-Meier and log-rank tests revealed that moderate (2+) to strong (3+) NFATc1 expression correlated with lower progression-free survival (P = .032) and cancer-specific survival (P = .005) rates in the 99 cases. Patients with high (2+/3+) NFATc1 muscle-invasive tumor (n = 9) also had a significantly higher risk of cancer-specific mortality (P = .021) compared to those with low (0/1+) NFATc1 muscle-invasive tumor (n = 53). Thus, compared with nonneoplastic urothelium, a significant increase in the expression of NFATc1 in UUTUC was seen, implying the involvement of NFATc1 signals in the development of UUTUC. The current results further suggest that NFATc1 overexpression serves as a predictor of poor prognosis in patients with UUTUC.     

Molecular Analysis of Upper Tract and Bladder Urothelial Carcinoma: Results from a Microarray Comparison

Introduction

Prior studies have shown genetic similarities between upper tract and bladder urothelial carcinoma. However, upper tract urothelial carcinoma tends to be higher grade than bladder urothelial carcinoma and tends to form in patients with certain familial conditions (e.g. Lynch Syndrome), indicating there may be unique biologic processes in these tumors. The purpose of this study was to evaluate the differences in gene expression between upper tract and bladder urothelial carcinoma using microarray data.

Design, Setting, Participants

A search of publicly available microarray datasets identified a clinically annotated dataset of 12 upper tract and 20 bladder urothelial carcinoma specimens. Gene expression analysis of data derived from the Affymetrix HGU133Plus2 chip was performed. Bioconductor packages were used to evaluate clustering, differential gene expression, pathways relevant to oncology, and a basal/luminal signature in upper tract versus bladder urothelial carcinoma.

Results

When separated by pathologic T stage, there was evidence of differential clustering among pT3 tumors and significant gene expression differences in 81 genes. Pathway analysis revealed differences in HGF and TNF signaling pathways. Upper tract tumors tended to have high expression of genes associated with a luminal subtype. One of the genes most highly expressed in upper tract tumors, SLITRK6, is the target of an antibody drug conjugate (AGS15E) currently in phase I clinical trials.

Conclusions

This study provides evidence for molecular differences between upper tract and bladder urothelial carcinoma, some of which contribute to oncologic-relevant pathways. Upper tract tumors tended to express genes consistent with a luminal subtype. We also identify a marker, SLITRK6, as a potential target for patients with advanced upper tract urothelial carcinoma.     

Upper and Lower Urinary Tract Outcomes in Adult Myelomeningocele Patients: A Systematic Review

Background

The introduction of sophisticated treatment of bladder dysfunction and hydrocephalus allows the majority of SB patients to survive into adulthood. However, no systematic review on urological outcome in adult SB patients is available and no follow-up schemes exist.

Objectives

To systematically summarize the evidence on outcome of urinary tract functioning in adult SB patients.

Methods

A literature search in PubMed and Embase databases was done. Only papers published in the last 25 years describing patients with open SB with a mean age >18 years were included. We focused on finding differences in the treatment strategies, e.g., clean intermittent catheterization and antimuscarinic drugs versus early urinary diversion, with regard to long-term renal and bladder outcomes.

Results

A total of 13 articles and 5 meeting abstracts on urinary tract status of adult SB patients were found describing a total of 1564 patients with a mean age of 26.1 years (range 3–74 years, with a few patients <18 years). All were retrospective cohort studies with relatively small and heterogeneous samples with inconsistent reporting of outcome; this precluded the pooling of data and meta-analysis. Total continence was achieved in 449/1192 (37.7%; range 8–85%) patients. Neurological level of the lesion and hydrocephalus were associated with incontinence. Renal function was studied in 1128 adult patients. In 290/1128 (25.7%; range 3–81.8%) patients some degree of renal damage was found and end-stage renal disease was seen in 12/958 (1.3%) patients. Detrusor-sphincter dyssynergy and detrusor-overactivity acted as adverse prognostic factors for the development of renal damage.

Conclusions

These findings should outline follow-up schedules for SB patients, which do not yet exist. Since renal and bladder deterioration continues beyond adolescence, follow-up of these individuals is needed. We recommend standardization in reporting the outcome of urinary tract function in adult SB patients.     

Diagnostic Ureterorenoscopy Is Associated with Increased Intravesical Recurrence following Radical Nephroureterectomy in Upper Tract Urothelial Carcinoma

Diagnostic ureterorenoscopy is powerful tool to confirm upper tract urothelial cancer (UTUC). However, URS and associated manipulation may be related to the risk of intravesical recurrence (IVR) following radical nephroureterectomy (RNU). We aimed to investigate whether preoperative ureterorenoscopy would increase IVR after RNU in patients with UTUC. We performed a retrospective analysis of 630 patients who had RNU with bladder cuff excision due to UTUC. Diagnostic URS was performed in 282 patients (44.7%). Patients were divided into two groups according to the URS. Survival analysis and multivariate Cox regression model were performed to address risk factors for the IVR. The interval from URS to RNU was measured. During URS, manipulation such as biopsy and resection was determined. The median age was 64 (IQR 56–72) years with follow-up duration of 34.3 (15.7–64.9) months. Median time from URS to RNU was 16 (0–38) days. The IVR developed in 42.5% (n = 268) patients at 8.2 (4.9–14.7) months. The five-year IVR-free survival rate was 42.6 ± 8.0% and 63.6 ± 6.9% in patients with and without preoperative URS, respectively (P < 0.001). In multivariate analysis, previous history of bladder tumour, extravesical excision of distal ureter, multifocal tumour, and URS (HR, 95% CI; 1.558, 1.204–2.016, P = 0.001) were independent predictors for higher IVR. The IVR rate in patients without manipulation during URS was not different to those with manipulation (P = 0.658). The duration from URS to RNU was not associated with IVR (P = 0.799). Diagnostic URS for UTUC increased IVR rate after RNU. However, the lessening of interval from URS to radical surgery or URS without any manipulation could not reduce the IVR rate.     

Concurrent Preoperative Presence of Hydronephrosis and Flank Pain Independently Predicts Worse Outcome of Upper Tract Urothelial Carcinoma

Objectives

To investigate the impact of preoperative hydronephrosis and flank pain on prognosis of patients with upper tract urothelial carcinoma.

Methods

In total, 472 patients with upper tract urothelial carcinoma managed by radical nephroureterectomy were included from Kaohsiung Medical University Hospital Healthcare System. Clinicopathological data were collected retrospectively for analysis. The significance of hydronephrosis, especially when combined with flank pain, and other relevant factors on overall and cancer-specific survival were evaluated.

Results

Of the 472 patients, 292 (62%) had preoperative hydronephrosis and 121 (26%) presented with flank pain. Preoperative hydronephrosis was significantly associated with age, hematuria, flank pain, tumor location, and pathological tumor stage. Concurrent presence of hydronephrosis and flank pain was a significant predictor of non-organ-confined disease (multivariate-adjusted hazard ratio = 2.10, P = 0.025). Kaplan-Meier analysis showed significantly poorer overall and cancer-specific survival in patients with preoperative hydronephrosis (P = 0.005 and P = 0.026, respectively) and in patients with flank pain (P < 0.001 and P = 0.001, respectively) than those without. However, only simultaneous hydronephrosis and flank pain independently predicted adverse outcome (hazard ratio = 1.98, P = 0.016 for overall survival and hazard ratio = 1.87, P = 0.036 for and cancer-specific survival, respectively) in multivariate Cox proportional hazards models. In addition, concurrent presence of hydronephrosis and flank pain was also significantly predictive of worse survival in patient with high grade or muscle-invasive disease. Notably, there was no difference in survival between patients with hydronephrosis but devoid of flank pain and those without hydronephrosis.

Conclusion

Concurrent preoperative presence of hydronephrosis and flank pain predicted non-organ-confined status of upper tract urothelial carcinoma. When accompanied with flank pain, hydronephrosis represented an independent predictor for worse outcome in patients with upper tract urothelial carcinoma.     

Preoperative Plasma Fibrinogen Level Represents an Independent Prognostic Factor in a Chinese Cohort of Patients with Upper Tract Urothelial Carcinoma

Background

Increased plasma fibrinogen is thought to contribute to tumor progression and metastasis. The association of plasma fibrinogen with clinicopathological characteristics, and the optimal cutoff with an ideal predictive value has not been fully determined in patients with upper tract urothelial carcinoma (UTUC). We aimed to investigate the clinical significance of this parameter in a Chinese cohort of patients with UTUC.

Methods

A retrospective study was conducted to analyze the clinical data of 184 operable UTUC patients in a Chinese cohort with a high incidence of chronic kidney disease (CKD). An optimal cutoff was set for further analysis according to validated web-based software. The associations of plasma fibrinogen with clinicopathological characteristics and survival were assessed. Multivariate analyses were performed to determine the independent prognostic factors.

Results

Elevated plasma fibrinogen was significantly associated with tumor necrosis, lymph node involvement, and a higher preoperative CKD stage, pathological tumor stage and grade (all P < 0.05). Kaplan-Meier analysis showed that plasma fibrinogen ≥ 3.54 g/L predicted a poorer overall and cancer-specific survival than < 3.54 g/L (P < 0.001 for both). Multivariate analyses revealed that elevated preoperative plasma fibrinogen was an independent negative prognostic factor for overall survival (HR = 2.026; 95% CI: 1.226–3.349; P = 0.006) and cancer-specific survival (HR = 1.886; 95% CI: 1.019–3.490; P = 0.043).

Conclusions

Increased plasma fibrinogen was an independent prognostic risk factor for poor outcomes in UTUC. This parameter may serve as an effective biomarker with easy accessibility for evaluating prognosis for patients with UTUC.     

Analysis of Tissue and Serum MicroRNA Expression in Patients with Upper Urinary Tract Urothelial Cancer

Introduction

MicroRNAs play an important role in many human malignancies; so far, their expression remains to be studied in upper urinary tract urothelial cancer (UUTUC).

Materials and Methods

The expression of eleven microRNAs (miR-10a, miR-21, miR-96, miR-135, miR-141, miR-182, miR-200b, miR-205, miR-429, miR-520b, miR-1244) formerly shown to be upregulated in urothelial bladder cancer were studied in corresponding normal and cancerous tissue samples of patients undergoing nephroureterectomy for UUTUC. Upregulated microRNAs were then measured in serum samples of patients with UUTUC and patients with non-malignant urological diseases to evaluate their potential as non-invasive biomarkers for UUTUC.

Results

MicroRNA expression allowed differentiation of normal and cancerous tissue: miR-21, miR-96, miR-135, miR-141, miR-182, miR-205, miR-429 and miR-520b were significantly overexpressed. Furthermore, miR-205 was upregulated in poorly differentiated UUTUC. The analysis of circulating RNA in serum demonstrated an increase of miR-141 in patients with UUTUC; receiver operator characteristic analysis demonstrated an area under the curve of 0.726 for miR-141 as a diagnostic biomarker. Furthermore, we observed lower levels of miR-10a and miR-135 in UUTUC patients.

Conclusions

MicroRNA expression is altered in UUTUC. The analysis of circulating miR-141 may be useful to identify patients with UUTUC.     

Long-Term Oncologic Outcomes of Laparoscopic versus Open Surgery for Middle and Lower Rectal Cancer

Background

Laparoscopic surgery for middle and lower rectal cancer remain controversial because anatomical and complex surgical procedures specifically influence oncologic outcomes. This study analyzes the long-term outcomes of laparoscopic versus open surgery for middle and lower rectal cancer.

Methods

Patients (laparoscopic: n = 129, open: n = 152) who underwent curative resection for middle and lower rectal cancer from 2003 to 2008 participated in the study. The same surgical team performed all operations. The mean follow up time of all patients was 74.3 months.

Results

No statistical difference in local recurrence rate (7.8% vs. 7.2%; log-rank = 0.024; P = 0.876) and distant recurrence rate (20.9% vs.16.4%; log-rank = 0.699; P = 0.403) between laparoscopic and open groups were observed within 5 years. The 5-year overall survival rates of the laparoscopic and open groups were 72.9% and 75.7%, respectively; no significant statistical difference was observed between them (log-rank = 0.163; P = 0.686). The 5-year survival rates between groups were not different between stages: Stage I (92.6% vs. 86.7%; log-rank = 0.533; P = 0.465); stage II (75.8% vs. 80.5%; log-rank = 0.212; P = 0.645); and Stage III (63.8% vs. 69.1%, log-rank = 0272;P = 0.602). However, significant statistical difference amongst different stages were observed (log-rank = 1.802; P = 0.003).

Conclusion

Laparoscopic and open surgery for middle and lower rectal cancer offer equivalent long-term oncologic outcomes. Laparoscopic surgery is feasible in these patients.     

The Prognostic Impact of Histopathological Variants in Patients with Advanced Urothelial Carcinoma

Purpose

This study investigated the prognostic role of histopathological variants in patients with advanced urothelial carcinoma (UC) who were treated with systemic chemotherapy.

Materials and Methods

We conducted a retrospective analysis of patients with unresectable and/or metastatic UC who underwent systemic chemotherapy between January 1997 and December 2013 in Kaohsiung Chang Gung Memorial Hospital. Histopathological types were categorized as pure UC (PUC) and variants of UC (VUC). The overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan–Meier analyses and Cox proportional regression models.

Results

A total of 206 patients were enrolled; 53 of the patients (25.7%) had histopathological variants. The most common variant was squamous differentiation (68%). Compared with patients with PUC, patients with VUC significantly exhibited upper urinary tract origin (75% vs 52%, P = .008), chronic renal insufficiency (40% vs 23%, P = .03), and carboplatin-based chemotherapy (28% vs 10%, P = .003). According to univariate analysis, the median OS for PUC patients was significantly higher than that for VUC patients (15.9 vs 11.3 months, P = .007). The median PFS for patients who received first-line chemotherapy was 6.1 and 3.8 months for PUC patients and VUC patients, respectively (P = .004). Multivariate analysis revealed that VUC (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.16–2.40, P = .006), an age ≤ 60 years (HR 0.70, 95% CI 0.49–0.99, P = .045) and presence of visceral metastasis (HR 1.54, 95% CI 1.11–2.13, P = .009) were independent factors facilitating OS prediction.

Conclusions

The presence of histopathological variants indicates poor survival outcomes in patients with metastatic UC. Accordingly, VUC should be integrated into and considered an independent factor in a predictive model of survival.     

性激素受体在膀胱肿瘤生存预后中的临床价值

目的:观察性激素受体(雄激素受体和雌激素β受体,AR和ERβ)在膀胱癌中的表达,通过它们与临床病理特征和术后复发预后的相关分析来探讨性激素受体的临床意义与价值。方法:采用免疫组织化学SP法检测AR和ERβ蛋白在64例膀胱尿路上皮癌的表达。显微镜下随机选取5个400×高倍视野,每个视野计数100个癌细胞中的阳性细胞数,通过计算染色阳性的细胞率来评估受体蛋白的表达情况。结果:两种性激素受体蛋白均阳性定位于细胞核中。AR阳性表达率为26.6%,ERβ阳性率为81.2%。AR和ERβ的阳性表达率在男女性别方面均无统计学差别(P=0.1982,0.0669)。随着膀胱癌病理分级升高,AR和ERβ的阳性表达率均增高(P=0.0182,0.0360)。同时,AR和ERβ的表达与患病年龄,膀胱内肿瘤数目,肿瘤大小,肿瘤的临床分期均无统计学相关性(P均>0.05)。术后随访患者时间为2-81月,生存分析显示:AR与肿瘤的复发间隔期和5年复发率相关(P=0.0442)。ERβ则与肿瘤患者的总生存期相关(P=0.0001)。阳性表达AR的患者,复发间隔时间增长,5年复发率较低;ERβ阳性患者总生存期较长。结论:性激素受体AR和ERβ阳性表达于临床膀胱癌组织中,并且均与膀胱癌的分化密切相关。这提示AR和ERβ可能在膀胱癌的发生发展中起一定作用。同时,两种蛋白还能作为评估膀胱癌复发预后的预测指标。     

Impact of Temperature on Upper Respiratory Tract Infections in Lanzhou Based on the Distributed Lag Model

The study mainly analyzed the relationship between temperature and the upper respiratory tract infections (URI) in Lanzhou. We collected the daily URI and meteorological data from 2010 to 2015. A distributed lag non-linear model was used to examine the relationship and potential effects of different temperatures and different lag days on the morbidity of URI. The results showed that the morbidity of URI was significantly related to the meteorological factors, and the peak of the onset of the disease usually occurred between November and February the next year. The correlation analysis was carried out between meteorological factors and URI cases, and the result revealed that the daily morbidity of URI in Lanzhou was related to air temperature, air pressure, and wind speed. The exposure effect curve of average daily temperature to different sex and different age groups in Lanzhou displayed an M-shaped. Temperature had a certain lag effect on the daily morbidity of URI. For low temperature, it appeared on the present day, and the maximum impact appeared at lag 2 days and persisted for 12 days. The female was more vulnerable than the male, and the impact was obvious in teenagers and the elderly and not obvious in adult. Meteorological factors play an important role in the occurrence of URI in Lanzhou, but the main factor is low temperature. Temperature can trigger the morbidity of URI directly; it can induce various symptoms of URI (such as cold, sore throat and rhinitis) and directly affect the distribution of URI in the population.     

Identification of ALK Gene Alterations in Urothelial Carcinoma

Background

Anaplastic lymphoma kinase (ALK) genomic alterations have emerged as a potent predictor of benefit from treatment with ALK inhibitors in several cancers. Currently, there is no information about ALK gene alterations in urothelial carcinoma (UC) and its correlation with clinical or pathologic features and outcome.

Methods

Samples from patients with advanced UC and correlative clinical data were collected. Genomic imbalances were investigated by array comparative genomic hybridization (aCGH). ALK gene status was evaluated by fluorescence in situ hybridization (FISH). ALK expression was assessed by immunohistochemistry (IHC) and high-throughput mutation analysis with Oncomap 3 platform. Next generation sequencing was performed using Illumina Genome Analyzer IIx, and Illumina HiSeq 2000 in the FISH positive case.

Results

70 of 96 patients had tissue available for all the tests performed. Arm level copy number gains at chromosome 2 were identified in 17 (24%) patients. Minor copy number alterations (CNAs) in the proximity of ALK locus were found in 3 patients by aCGH. By FISH analysis, one of these samples had a deletion of the 5′ALK. Whole genome next generation sequencing was inconclusive to confirm the deletion at the level of the ALK gene at the coverage level used. We did not observe an association between ALK CNA and overall survival, ECOG PS, or development of visceral disease.

Conclusions

ALK genomic alterations are rare and probably without prognostic implications in UC. The potential for testing ALK inhibitors in UC merits further investigation but might be restricted to the identification of an enriched population.     

肺鳞癌、腺癌组织中miRNA-210表达对预后影响的初步研究

目的:探讨肺鳞癌腺癌组织中mi RNA-210表达水平对预后的影响。方法:选取我院2004年至2007年接受手术治疗的肺鳞癌腺癌患者80例,采用定量RT-PCR测定的方法 mi RNA-210在肺癌组织中的表达,并分析其与患者临床病理特点及组织类型之间的关系。结果:定量RT-PCR测定结果显示,mi RNA-210与肺鳞癌腺癌患者的无病生存期和总生存期负相关(DFS,P=0.001;OS,P=0.004)。mi RNA-210与腺癌患者淋巴结转移(P=0.018)、晚期疾病(P=0.003)及较差的预后(P=0.002)显著相关。多因素Cox分析显示mi RNA-210是腺癌患者无病生存期的独立预后因子(P0.001)。结论:肺腺癌病人肿瘤组织重mi RNA-210可能为预后的生物标志物。     

The 12p13.33/RAD52 Locus and Genetic Susceptibility to Squamous Cell Cancers of Upper Aerodigestive Tract

Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04–1.15, p = 6x10⁻⁴). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10⁻³) and LUSC (p = 9x10⁻⁴) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10⁻⁴⁸ and p = 3x10⁻²⁹ in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.