Tumor polo-like kinase 4 protein expression reflects lymphovascular invasion, higher Federation of Gynecology and Obstetrics stage, and shortened survival in endometrial cancer patients who undergo surgical resection.

BACKGROUND: Polo-like kinase 4 (PLK4) serves as a marker for tumor features and poor outcomes in cancers. This study aimed to explore the associations of tumor PLK4 protein expression with tumor characteristics and survival in endometrial cancer (EC) patients who underwent surgical resection. METHODS: This study included 142 EC patients who underwent surgical resection. Tumor tissue samples were obtained for tumor PLK4 protein expression detection via immunohistochemistry (IHC). RESULTS: Among EC patients, 26.1% had a PLK4 IHC score of 0, 24.6% had a score of 1-3, 27.5% had a score of 4-6, and 21.8% had a score of 7-12. Tumor PLK4 protein expression positively associated with lymphovascular invasion (P = 0.008) and Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.005). Disease-free survival (DFS) was not different between patients with tumor PLK4 IHC scores > 0 and ≤ 0 (P = 0.154) but was reduced in patients with scores > 3 vs. ≤ 3 (P = 0.009) and > 6 vs. ≤ 6 (P < 0.001). Similarly, overall survival (OS) was not different between patients with scores > 0 and ≤ 0 (P = 0.322) but was shorter in patients with scores > 3 vs. ≤ 3 (P = 0.011) and > 6 vs. ≤ 6 (P = 0.006). After adjustment, a tumor PLK4 IHC score > 6 (vs. ≤ 6) (hazard ratio (HR): 3.156, P = 0.008) or > 3 (vs. ≤ 3) (HR: 3.918, P = 0.026) was independently associated with shortened DFS and OS. CONCLUSION: A tumor PLK4 IHC score > 6 or > 3 associates with shortened DFS and OS in EC patients who undergo surgical resection.

Routine and interval detection of locoregional breast cancer recurrences and risk of subsequent distant metastasis.

PURPOSE: Follow-up for breast cancer survivors consists of after care and surveillance. The benefits of routine surveillance visits remain debatable. In this study we compared the severity of locoregional recurrences (LRRs) and the subsequent risk of a distant metastasis (DM) between LRRs detected at routine and interval visits. METHODS: Women diagnosed with early breast cancer between 2003 and 2008 in one of the 15 participating hospitals, and who developed a LRR as first event after primary treatment, were selected from the Netherlands Cancer Registry (Cohort A). Chi-squared tests were used to compare the severity of routine- and interval-detected local recurrences (LRs) and regional recurrences (RRs), using tumor size, tumor grade, and number of positive lymph nodes. Data on the development of a subsequent DM after a LRR were available for a subset of patients (Cohort B). Cohort B was used to estimate the association between way of LRR-detection and risk of a DM. RESULTS: Cohort A consisted of 109 routine- and 113 interval-LRR patients. The severity of routine-detected LRs or RRs and interval-detected LRs or RRs did not significantly differ. Cohort B consisted of 66 routine- and 61 interval-LRR patients. Sixteen routine- (24%) and 17 (28%) interval-LRR patients developed a DM. After adjustment, way of LRR-detection was not significantly associated with the risk of a DM (hazard ratio: 1.22; 95% confidence interval: 0.49-3.06). CONCLUSION: The current study showed that routine visits did not lead to less severe LRRs and did not decrease the risk of a subsequent DM.

Prolonged screening interval due to the COVID-19 pandemic and its association with tumor characteristics and treatment; a register-based study from BreastScreen Norway.

OBJECTIVE: During the COVID-19 pandemic Norway had to suspend its national breast cancer screening program. We aimed to investigate the effect of the pandemic-induced suspension on the screening interval, and its subsequent association with the tumor characteristics and treatment of screen-detected (SDC) and interval breast cancer (IC). METHODS: Information about women aged 50-69, participating in BreastScreen Norway, and diagnosed with a SDC (N = 3799) or IC (N = 1806) between 2018 and 2021 was extracted from the Cancer Registry of Norway. Logistic regression was used to investigate the association between COVID-19 induced prolonged screening intervals and tumor characteristics and treatment. RESULTS: Women with a SDC and their last screening exam before the pandemic had a median screening interval of 24.0 months (interquartile range: 23.8-24.5), compared to 27.0 months (interquartile range: 25.8-28.5) for those with their last screening during the pandemic. The tumor characteristics and treatment of women with a SDC, last screening during the pandemic, and a screening interval of 29-31 months, did not differ from those of women with a SDC, last screening before the pandemic, and a screening interval of 23-25 months. ICs detected 24-31 months after screening, were more likely to be histological grade 3 compared to ICs detected 0-23 months after screening (odds ratio: 1.40, 95% confidence interval: 1.06-1.84). CONCLUSIONS: Pandemic-induced prolonged screening intervals were not associated with the tumor characteristics and treatment of SDCs, but did increase the risk of a histopathological grade 3 IC. This study provides insights into the possible effects of extending the screening interval.

Clinical Implication of Keratin-15 Quantification for Renal Cell Carcinoma Management: Its Dysregulation and Association with Clinicopathologic Characteristics and Prognostication.

Keratin-15 (KRT15) participates in the tumorigenesis of several cancers, especially in urinary tract carcinomas by regulating basal urothelial cell malignant proliferation and differentiation. This study intended to explore the association of KRT15 with tumor features and survival in renal cell carcinoma (RCC) patients. Totally, 210 RCC patients receiving surgical resection were retrospectively enrolled, and then, KRT15 was detected by immunohistochemistry (IHC) assay in the tumor and adjacent tissues. IHC score of KRT15 was increased in tumor tissues versus adjacent tissues (P < 0.001). Meanwhile, KRT15 was associated with RCC occurring in the left kidney (P = 0.024), tumor size > 10 cm (P = 0.035), higher N stage (P = 0.048), and higher tumor-node-metastasis (TNM) stage (P = 0.029). Additionally, high KRT15 (IHC score > 3) estimated poor disease-free survival (DFS) (P = 0.008) and overall survival (OS) (P = 0.011). In addition, multivariate regression analysis revealed that high KRT15 [hazard ratio (HR) = 1.719, P = 0.023], higher pathological grade (HR = 1.847, P < 0.001), and higher N stage (HR = 3.447, P < 0.001) were independently related to poor DFS; high KRT15 (HR = 1.796, P = 0.034), eastern cooperative oncology group performance status score (1 vs. 0) (HR = 1.734, P = 0.037), higher pathological grade (HR = 2.045, P < 0.001), and higher N stage (HR = 3.966, P < 0.001) were independently linked to unsatisfactory OS. Furthermore, data from Gene Expression Profiling Interactive Analysis suggested that KRT15 was linked to poor DFS (P = 0.037) and OS (P < 0.001); data from THE HUMAN PROTEIN ATLAS revealed that KRT15 was associated with shorter OS (P < 0.001) in RCC patients. In conclusion, KRT15 is increased in tumor tissues, and correlates with higher tumor stage and larger tumor size, along with poor prognosis for RCC.

Breast cancer and cardiovascular outcomes after breast cancer in survivors of Hodgkin lymphoma.

BACKGROUND: Hodgkin lymphoma (HL) survivors treated with chest radiotherapy have an increased risk of breast cancer (BC). Prior HL treatment and associated cardiovascular disease (CVD) risk may limit BC treatment options. It is unknown how treatment adaptations affect BC and CVD outcomes. METHODS: The authors compared 195 BC patients treated with chest/axillary radiotherapy for HL (BC-HL) with 5988 age- and calendar year-matched patients with first primary BC (BC-1). Analyses included cumulative incidence functions and Cox regression models, accounting for tumor characteristics and BC treatment. RESULTS: Compared to BC-1 patients, BC-HL patients received anthracycline-containing chemotherapy (23.7% vs. 43.8%, p < .001) and breast-conserving surgery followed by radiotherapy (7.1% vs. 57.7%, p < .001) less often. BC treatment considerations were reported for 71% of BC-HL patients. BC-HL patients had a significantly higher risk of 15-year overall mortality than BC-1 patients (61% vs. 23%). Furthermore, risks of BC-specific mortality and nonfatal BC events were significantly increased among BC-HL patients, also when accounting for tumor and treatment characteristics (2.2- to 4.5-fold). BC-HL patients with a screen-detected BC had a significantly reduced (61%) BC-specific mortality. One-third of BC-HL patients had CVD at BC-diagnosis, compared to <0.1% of BC-1 patients. Fifteen-year CVD-specific mortality and CVD incidence were significantly higher in BC-HL patients than in BC-1 patients (15.2% vs. 0.4% and 40.4% vs. 6.8%, respectively), which was due to HL treatment rather than BC treatment. CONCLUSIONS: BC-HL patients experience a higher burden of CVD and worse BC outcomes than BC-1 patients. Clinicians should be aware of increased CVD risk when selecting BC treatment for HL survivors. LAY SUMMARY: Patients with breast cancer after Hodgkin lymphoma (BC-HL) may have limited options for BC treatment, due to earlier HL treatment and an associated increased risk of cardiovascular disease (CVD). BC treatment considerations were reported for 71% of BC-HL patients. We examined whether BC-HL patients have a higher risk of CVD or BC events (recurrences/metastases) compared to patients with breast cancer that had no earlier tumors (BC-1). We observed a higher burden of CVD and worse BC outcomes in HL patients compared to BC-1 patients. Clinicians should be aware of increased CVD risk when selecting BC treatment for HL survivors.

Characterizing isolated tumor cells in regional lymph nodes of early endometrial cancer.

OBJECTIVE: To examine the characteristics of isolated tumor cells (ITCs) in regional lymph nodes of early-stage endometrial cancer. METHODS: This is a retrospective cohort study examining the National Cancer Institute's Surveillance, Epidemiology, and End Result Program. The study population was 6472 women with non-metastatic, node-negative T1 endometrial cancer who underwent primary hysterectomy and surgical nodal evaluation. Multivariable binary logistic regression model was used to identify the independent characteristics for ITCs. Postoperative therapy according to ITCs status was also assessed with propensity score weighting. RESULTS: ITCs were seen in 111 (1.7%) cases. In a multivariable analysis, ITCs were largely associated with tumor factors including deep myometrial invasion (T1b versus T1a, 4.0% versus 1.0%, adjusted-odds ratio [aOR] 3.42, P < 0.001) and larger tumor size (>4 versus ≤4 cm, 3.0% versus 1.6%, aOR 1.55, P = 0.037). Moreover, women undergoing sentinel lymph node (SLN) biopsy had a higher likelihood of identifying ITCs compared to those undergoing lymphadenectomy (LND): 2.7% for SLN alone, 3.7% for SLN/LND, and 1.2% for LND alone (aOR ranged 2.60-2.99, P < 0.001). Women who had ITCs identified were more likely to receive postoperative therapy (81.8% versus 31.7%, P < 0.001), including external beam radiotherapy (EBT) alone (25.1% versus 3.2%) and chemotherapy/EBT (16.3% versus 1.9%). Similar associations were observed in the low-risk group (stage IA, grade 1-2 endometrioid, 78.4% versus 9.2%, P < 0.001), including EBT alone (35.3% versus 0.6%). CONCLUSION: This study suggests that a SLN protocol can identify more ITCs in the regional lymph nodes of early endometrial cancer. Deep myometrial invasion and large tumor size were associated with increased risk of ITCs. Postoperative therapy is offered more frequently in the setting of ITCs with variable treatment patterns, warranting further outcome studies and practice guidelines.

Preoperative aspartate aminotransferase to albumin ratio correlates with tumor characteristics and predicts outcome of hepatocellular carcinoma patients after curative hepatectomy: a multicenter study.

AIMS: This study aimed to evaluate the clinical significance of the preoperative aminotransferase to albumin ratio (AAR) in patients with hepatocellular carcinoma (HCC) after hepatectomy. METHODS: From five hospitals, a total of 991 patients with HCC admitted between December 2014 and December 2019 were included as the primary cohort and 883 patients with HCC admitted between December 2010 and December 2014 were included as the validation cohort. The X-tile software was conducted to identify the optimal cut-off value of AAR. RESULTS: In the primary cohort, the optimal cut-off value of the AAR was defined as 0.7 and 1.6, respectively. Compared to patients with AAR 0.7-1.6, those with AAR > 1.6 showed significantly worse overall survival (OS) and RFS, whereas those with AAR < 0.7 showed significantly better OS and RFS (all p < 0.001). Pathologically, patients with AAR > 1.6 had more aggressive tumour characteristics, such as larger tumour size, higher incidence of microvascular invasion, and severe histologic activity, and higher AFP level than patients with AAR < 0.7. Consistently, the abovementioned clinical significance of AAR was confirmed in the validation cohort. CONCLUSIONS: A high AAR was significantly correlated with advanced tumours and severe hepatic inflammation, and a worse prognosis of HCC.

Low thyroid hormone receptor alpha-2 (THRα-2) tumor expression is associated with unfavorable tumor characteristics and high breast cancer mortality.

BACKGROUND: The active thyroid hormone triiodothyronine (T3) has been found to have an estrogen-like effect on breast cancer cells. Thyroid hormone receptor alpha-2 (THRα-2) acts as an antagonist for triiodothyronine (T3) signaling, and a low expression has been associated with unfavorable tumor characteristics and a higher mortality in breast cancer. However, the evidence are not conclusive. The present study evaluates tumor-specific THRα-2 expression in invasive breast cancers and its association with tumor characteristics and long-term mortality in a large population. METHOD: The Malmö Diet and Cancer Study (MDCS), a population-based cohort in Sweden that included 17,035 women from 1991 to 1996, was used. Women diagnosed with breast cancer during 1991-2010 were eligible for inclusion. A tissue micro array was constructed from stored tumor material and stained for THRα-2 using immunohistochemistry. Tumors from 654 patients were scored regarding the intensity and the fraction of cells stained, then dichotomized into low or high expression. Date and cause of death were collected up until 2018-12-31. Tumor- and patient characteristics were available from the MDCS. Missing data was imputed using chained equations. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for low vs high expression of THRα-2 related to specific tumor factors. Mortality was evaluated with Kaplan-Meier curves and Cox regression, rendering hazard ratios (HRs). Analyses were also stratified for estrogen receptor (ER) status. RESULTS: We found strong evidence of an association between low THRα-2 and unfavorable tumor characteristics, including estrogen receptor negativity: OR 4.04 (95% CI 2.28-7.15) and tumor size > 20-50 mm: OR 2.20 (95% CI 1.39-3.49). We found evidence of increased breast cancer-specific mortality for women with low THRα-2, HR 1.38 (95% CI 0.96-1.99), which remained after adjusting for age at diagnosis, HR 1.48 (95% CI 1.03-2.14), but not after adjusting for relevant prognostic factors, HR 0.98 (95% CI 0.66-1.45). THRα-2 expression in ER-negative tumors had an inverse correlation with overall mortality, HR 0.27 (95% CI 0.11-0.65). CONCLUSION: Low tumor-specific THRα-2 expression was in this study associated with prognostically unfavorable tumor characteristics and a higher mortality in breast cancer, but not independent from other prognostic factors.

Risk factors for breast cancer development by tumor characteristics among women with benign breast disease.

BACKGROUND: Among women diagnosed with invasive breast cancer, 30% have a prior diagnosis of benign breast disease (BBD). Thus, it is important to identify factors among BBD patients that elevate invasive cancer risk. In the general population, risk factors differ in their associations by clinical pathologic features; however, whether women with BBD show etiologic heterogeneity in the types of breast cancers they develop remains unknown. METHODS: Using a nested case-control study of BBD and breast cancer risk conducted in a community healthcare plan (Kaiser Permanente Northwest), we assessed relationships of histologic features in BBD biopsies and patient characteristics with subsequent breast cancer risk and tested for heterogeneity of associations by estrogen receptor (ER) status, tumor grade, and size. The study included 514 invasive breast cancer cases (median follow-up of 9 years post-BBD diagnosis) and 514 matched controls, diagnosed with proliferative or non-proliferative BBD between 1971 and 2006, with follow-up through mid-2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using multivariable polytomous logistic regression models. RESULTS: Breast cancers were predominantly ER-positive (86%), well or moderately differentiated (73%), small (74% < 20 mm), and stage I/II (91%). Compared to patients with non-proliferative BBD, proliferative BBD with atypia conferred increased risk for ER-positive cancer (OR = 5.48, 95% CI = 2.14-14.01) with only one ER-negative case, P-heterogeneity = 0.45. The presence of columnar cell lesions (CCLs) at BBD diagnosis was associated with a 1.5-fold increase in the risk of both ER-positive and ER-negative tumors, with a 2-fold increase (95% CI = 1.21-3.58) observed among postmenopausal women (56%), independent of proliferative BBD status with and without atypia. We did not identify statistically significant differences in risk factor associations by tumor grade or size. CONCLUSION: Most tumors that developed after a BBD diagnosis in this cohort were highly treatable low-stage ER-positive tumors. CCL in BBD biopsies may be associated with moderately increased risk, independent of BBD histology, and irrespective of ER status.

Allostatic score and its associations with demographics, healthy behaviors, tumor characteristics, and mitochondrial DNA among breast cancer patients.

INTRODUCTION: Allostatic load (AL), a composite index, has been used to capture variation in life-course stresses. However, few studies have been carried out among breast cancer patients. METHODS: In this study, we examined the cross-sectional association of AL with demographics, healthy behaviors, tumor characteristics, and mitochondrial DNA copy number in breast cancer patients. The study used a sub-sample of 934 women with newly diagnosed breast cancer at M.D. Anderson from 2013 to 2018. To construct the AL score, the study used a battery of seventeen factors that represents the activity of five physiological systems: metabolic, cardiovascular, immunological, renal, and liver. RESULTS: AL was positively associated with the age of disease diagnosis (P = 0.002), and was higher in Black and Hispanic populations than White (P = 0.001 and 0.032, respectively). AL was also found more abundant in those who experienced marital dissolution (P = 0.006), lacked a college education (P = 0.045), currently smoked (P = 0.011), and had low levels of physical activity (P = 0.037) than their counterparts. The study then found that higher AL was associated with increased odds of having poorly differentiated tumors (Odds ratio (OR): 1.40, 95% confidence interval (CI): 1.28, 1.62). An additional significant association was observed between AL with estrogen receptor negative (ER-) (OR = 1.56, 95%CI: 1.02, 2.36) among Black patients. Finally, we observed a significant positive correlation between AL with leukocyte mitochondrial DNA copy number variation (P < 0.001). CONCLUSIONS: We conclude AL is influenced by selected demographics and healthy behaviors, and further is correlated with tumor characteristics and mitochondrial DNA copy number in breast cancer patients.

Risk factors for contralateral breast cancer in postmenopausal breast cancer survivors in the NIH-AARP Diet and Health Study.

PURPOSE: The role of established breast cancer risk factors and clinical characteristics of the first breast cancer in the development of contralateral breast cancer (CBC) among postmenopausal women is unclear. METHODS: We identified 10,934 postmenopausal women diagnosed with a first primary breast cancer between 1995 and 2011 in the NIH-AARP Diet and Health Study. CBC was defined as a second primary breast cancer diagnosed in the contralateral breast ≥ 3 months after the first breast cancer. Exposures included pre-diagnosis risk factors (lifestyle, reproductive, family history) and clinical characteristics of the first breast cancer. We used multivariable Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over a median follow-up of 6.8 years, 436 women developed CBC. We observed an increasing trend in CBC risk by age (p-trend = 0.002) and decreasing trend by year of diagnosis (p-trend = 0.001) of the first breast cancer. Additional risk factor associations were most pronounced for endocrine therapy (HR 0.68, 95% CI 0.53-0.87) and family history of breast cancer (HR 1.38, 95% CI 1.06-1.80, restricted to invasive first breast cancer). No associations were found for lifestyle (body mass index, physical activity, smoking, alcohol) or reproductive factors (age at menarche, parity, age at first birth, age at menopause). CONCLUSIONS: This study suggests that clinical characteristics of the first breast cancer and family history of breast cancer, but not pre-diagnosis lifestyle and reproductive factors, are strongly associated with CBC risk among postmenopausal women. Future studies are needed to understand how these factors contribute to CBC etiology and to identify further opportunities for prevention.

The Impact of Exogenous Estrogen Exposure on the Characteristics and Outcome of Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Early-Stage Breast Cancer.

INTRODUCTION: The impact of exogenous estrogen exposure on breast cancer characteristics and outcomes is not well described. We aimed to investigate the effect of prior treatment with oral contraceptives (OCT), hormone replacement therapy (HRT), and fertility treatments on early-stage, estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. METHODS: This is a single-center retrospective cohort study comprising all women with ER-positive, HER2-negative, early breast cancer whose tumors were sent to Oncotype DX analysis between 2005 and 2012. Data on prior exposures to OCT, HRT, and fertility treatments were collected. The impact of these exposures on prespecified histopathological features was assessed including tumor size, nodal status, intensity of the hormonal receptors, grade, Oncotype recurrence score, Ki67, and lymphovascular and perineural invasion. The impact of these exposures on disease-free survival (DFS) and overall survival (OS) was also evaluated. RESULTS: A total of 620 women were included, of which 19% had prior exposure to OCT, 30% to HRT, and 11% to fertility treatments. OCT use was associated with smaller (≤1 cm) tumors (p = 0.023) and were less likely to have grade 3 disease (p = 0.049). No other associations were found between exogenous estrogen exposure and tumor characteristics. Median follow-up was 10.4 years. Ten-year DFS was 85.7%, and it was not influenced by exogenous exposure. Ten-year OS was 90.2%, and OCT was associated with improved OS in univariate analysis (HR = 0.31, 95% CI: 0.11-0.85), but this difference did not remain significant in multivariate analysis (p = 0.275). CONCLUSION: The impact of exogenous estrogen exposure on ER-positive, HER2-negative early breast cancer characteristics is limited. In the long term, none of the evaluated exposures had negative effect on DFS and OS.

CCT6A may act as a potential biomarker reflecting tumor size, lymphatic metastasis, FIGO stage, and prognosis in cervical cancer patients.

OBJECTIVE: Chaperonin-containing tailless complex polypeptide subunit 6A (CCT6A) is a critical regulator and newly identified clinical biomarker of several cancers, while its correlation with the clinical characteristics and prognosis of cervical cancer patients is unclear. Therefore, this study aimed to explore this issue. METHODS: Chaperonin-containing tailless complex polypeptide subunit 6A expression in tumor and tumor-adjacent tissues from 198 cervical cancer patients who underwent resection were detected by immunohistochemistry assay and reverse transcription-quantitative polymerase chain reaction. Besides, the clinicopathological features and survival data of cervical cancer patients were collected. RESULTS: Chaperonin-containing tailless complex polypeptide subunit 6A protein and mRNA levels were both increased in tumor tissues compared with tumor-adjacent tissues (both p < 0.001). Receiver operating characteristic curves showed that CCT6A protein (AUC: 0.774, 95% CI: 0.729-0.819) and mRNA levels (AUC: 0.904, 95% CI: 0.874-0.934) well discriminated tumor tissues from tumor-adjacent tissues. Besides, correlation analyses found that CCT6A protein and mRNA levels were positively correlated with lymph node metastasis and FIGO stage (all p < 0.05), apart from which CCT6A mRNA level was also positively associated with tumor size (p = 0.032). In addition, CCT6A protein and mRNA levels were negatively correlated with accumulating disease-free survival (both p < 0.05); meanwhile CCT6A mRNA level was negatively associated with accumulating overall survival as well (p = 0.010). CONCLUSION: Chaperonin-containing tailless complex polypeptide subunit 6A is elevated in tumor tissues, and its high expression associates with larger tumor size, lymph node metastasis, higher FIGO stage, and worse prognosis in cervical cancer patients.

Higher circular RNA_0015278 correlates with absence of extrathyroidal invasion, lower pathological tumor stages, and prolonged disease-free survival in papillary thyroid carcinoma patients.

BACKGROUND: Circular RNA_0015278 (circ_0015278) inhibits the progression of several cancers and is greatly reduced in papillary thyroid carcinoma (PTC) tissues compared with benign thyroid lesions by microarray profiling. This study aimed to further investigate the correlation of circ_0015278 with tumor characteristics and prognosis in PTC patients. METHODS: Totally, 206 PTC patients who underwent tumor resection were retrospectively enrolled; subsequently, circ_0015278 expression in their tumor and adjacent tissues was detected by reverse transcriptional-quantitative polymerase chain reaction. Besides, disease-free survival (DFS) and overall survival (OS) were calculated. RESULTS: Circ_0015278 was reduced in tumor tissues compared with adjacent tissues (p < 0.001), and receiver operating characteristic analysis showed that it well discriminated tumor tissues from adjacent tissues (area under curve: 0.903, 95% confidence interval: 0.874-0.932). Besides, higher tumor circ_0015278 expression was correlated with absence of extrathyroidal invasion (p = 0.036), lower pathological tumor (pT) stage (p = 0.05), pathological node (pN) stage (p = 0.002), and pathological tumor-node-metastasis (pTNM) stage (p = 0.001). Moreover, higher tumor circ_0015278 expression was associated with a reduced relapse rate (p = 0.011), but not mortality rate (p = 0.110); meanwhile, it was also correlated with prolonged DFS (p = 0.017), but not OS (p = 0.136). Additionally, multivariate Cox's regression analyses showed that higher tumor circ_0015278 expression independently associated with favorable DFS (p = 0.026, hazard ratio = 0.529). CONCLUSION: Circ_0015278 is reduced in tumor tissues, while its' higher expression in tumor correlates with absence of extrathyroidal invasion, lower pT, pN, and pTNM stage, as well as prolonged DFS in PTC patients.

Coexistence of papillary thyroid carcinoma in secondary hyperparathyroidism.

BACKGROUND: The coexistence of primary hyperparathyroidism and papillary thyroid carcinoma (PTC) is common and may be associative with more aggressive PTC, with higher rates of extrathyroidal extension and multicentricity. However, it is unclear whether secondary hyperparathyroidism (SHPT) is associated with more invasive PTC in terms of morbidity, tumor pathological characteristics, and prognosis. The aim of this study was to evaluate the rate and tumor characteristics of PTC in patients with SHPT. METHODS: A total of 531 patients diagnosed with SHPT who underwent surgery from August 2013 to December 2018 at the First Affiliated Hospital of Zhejiang University were evaluated retrospectively. Patient demographics, surgical records, and follow-up information were recorded and analyzed. Control subjects were matched to the enrolled patients in a 1:4 ratio in terms of age, sex and pathological subtype. RESULTS: Among the 531 patients with SHPT who underwent surgery, 34 had coexisting PTC and PTC + SHPT (6.4%). The mean tumor diameter in the PTC + SHPT group was smaller than that in the PTC group (5.57 mm vs 9.00 mm, p < 0.001). The proportion of papillary thyroid micro-carcinoma in the PTC + SHPT group was significantly higher than that in the PTC group (29 [85.29%] vs. 86[63.24%], p = 0.014). There were no statistically significant differences between groups in terms of tumor multicentricity (15 [44.12%] vs 39 [28.68%], p = 0.066), tumor bilaterality (9 [26.47%] vs. 29 [21.32%], p = 0.499), tumor extrathyroidal extension (2 [5.88%] vs. 19 [13.97%], p = 0.255), or lymph node (LN) metastasis rate (12 [35.29%] vs. 49 [36.03%], p = 1.000). However, the PTC + SHPT and PTC groups were significantly different in terms of contralateral thyroidectomy (10 [29.41%] vs. 70 [51.47%], p = 0.023) and lymph node dissection (22 [64.71%] vs. 125 [91.91%], p < 0.001).There was no significant difference between the PTC + SHPT and PTC groups in terms of prognostic staging (33 [97.06%] vs. 122 [89.71%], p = 0.309) or recurrence (mean follow-up time: 36 months vs. 39 months, p = 0.33). CONCLUSIONS: The prevalence of PTC is high in patients with SHPT; compared with PTC in the general population, most papillary thyroid carcinomas with SHPT are occult thyroid carcinomas and present no significant difference in terms of tumor pathological features and prognostic staging. It is necessary for surgeons to perform more adequate preoperative examination and be more careful during surgery to avoid missing the coexistence of PTC in patients with SHPT.

Gut microbiome associations with breast cancer risk factors and tumor characteristics: a pilot study.

OBJECTIVE: To investigate the association between gut microbiome with breast tumor characteristics (receptor status, stage and grade) and known breast cancer risk factors. METHODS: In a pilot cross-sectional study of 37 incident breast cancer patients, fecal samples collected prior to chemotherapy were analyzed by 16S ribosomal RNA (rRNA) gene-based sequencing protocol. Alpha diversity and specific taxa by tumor characteristics and breast cancer risk factors were tested by Wilcoxon rank sum test, and by differential abundance analysis, using a zero-inflated negative binomial regression model with adjustment for total counts, age and race/ethnicity. RESULTS: There were no significant alpha diversity or phyla differences by estrogen/progesterone receptor status, tumor grade, stage, parity and body mass index. However, women with human epidermal growth factor receptor 2 positive (HER2+) (n = 12) compared to HER2- (n = 25) breast cancer showed 12-23% lower alpha diversity [number of species (OTU) p = 0.033, Shannon index p = 0.034], lower abundance of Firmicutes (p = 0.005) and higher abundance of Bacteroidetes (p = 0.089). Early menarche (ages ≤ 11) (n = 11) compared with later menarche (ages ≥ 12) (n = 26) was associated with lower OTU (p = 0.036), Chao1 index (p = 0.020) and lower abundance of Firmicutes (p = 0.048). High total body fat (TBF) (> 46%) (n = 12) compared to lower (≤ 46%) TBF was also associated with lower Chao 1 index (p = 0.011). There were other significant taxa abundance differences by HER2 status, menarche age, as well as other tumor and breast cancer risk factors. CONCLUSIONS AND RELEVANCE: Further studies are needed to identify characteristics of the human microbiome and the interrelationships between breast cancer hormone receptor status and established breast cancer risk factors.

Assessment of stromal tumor infiltrating lymphocytes and immunohistochemical features in invasive micropapillary breast carcinoma with long-term outcomes.

PURPOSE: We studied the long-term outcomes of invasive micropapillary carcinoma (IMPCs) of the breast in relation to stromal tumor infiltrating lymphocytes (sTILs), prognostic biomarkers and clinicopathological features. METHODS: Stage I-III IMPCs treated with upfront surgery at our institution (January 2000 and December 2016) were included. Central pathology review was performed and sTILs (including zonal distribution and hot spot analysis) and tumor-associated plasma cells (TAPC) were evaluated. Expression of P53, BCL2, FOXP3, and WT1, which are variably linked to breast cancer prognosis, was measured by immunohistochemistry using tissue microarrays. Time-to-event endpoints were distant recurrence free interval (DRFI) and breast cancer-specific survival (BCSS). RESULTS: We included 111 patients of whom 59% were pure IMPCs. Standard clinicopathological features were comparable between pure and non-pure IMPCs. Overall, the mean sTILs level was 20% with higher proportion of sTILs present at the invasive front. There were no significant differences between pure- and non-pure IMPCs in sTILs levels, nor in the spatial distribution of the hot spot regions or in the distribution of TAPC. Higher sTILs correlated with worse DRFI (HR = 1.55; p = 0.0172) and BCSS (HR = 2.10; p < 0.001). CONCLUSIONS: Clinicopathological features, geographical distribution of sTILs and TAPC are similar between pure and non-pure IMPCs. Despite a high proportion of grade 3 tumors and lymph node involvement, we observed a low rate of distant recurrences and breast cancer-related death in this cohort of stage I-III IMPCs treated with primary surgery. Caution in interpretation of the observed prognostic correlations is required given the very low number of events, warranting validation in other cohorts.

Tumor characteristics, treatments, and survival outcomes in prostate cancer patients with a PSA level < 4 ng/ml: a population-based study.

BACKGROUND: To examine the tumor characteristics, treatments and survival outcomes of prostate cancer (PCa) patients with a prostate-specific antigen (PSA) level < 4 ng/ml. METHODS: Of 205,913 men with primary prostate adenocarcinoma in the Surveillance, Epidemiology and End Results (SEER) database (2010 to 2015), 24,054 (11.68%) patients were diagnosed with a PSA level < 4 ng/ml. Comparisons of categorical variables among different groups were performed by using the Chi square test. Multivariate Cox regression analysis was adjusted for age, ethnicity, marital status, insurance status, TNM stage, Gleason grade, treatment and survival. Kaplan-Meier survival curves were constructed for overall mortality and tested by the log-rank test. RESULTS: PCa patients with a PSA level < 4 ng/ml generally had more favorable tumor characteristics: younger, lower T stage, lower Gleason grade and lower lymph node metastasis rate. However, there were more patients in stage M1 in the group of PSA level < 4 ng/ml than that in the groups of PSA level of 4-10 ng/ml, 10-20 ng/ml and > 20 ng/ml. The multivariate Cox regression model revealed that overall mortality was associated with age, marital status, race, Gleason grade, M stage and treatment approach. CONCLUSIONS: In conclusion, PCa patients with a PSA level < 4 ng/ml have more favorable tumor characteristics at diagnosis and receive more benefit from active treatment. However, those patients with advanced TNM stage and high Gleason grade should be paid more attention in clinical application.

Contemporary conditional cancer-specific survival after radical nephroureterectomy in patients with nonmetastatic urothelial carcinoma of upper urinary tract.

BACKGROUND AND OBJECTIVES: To examine the effect of conditional survival on 5-year cancer-specific survival (CSS) probability after radical nephroureterectomy (RNU) in a contemporary cohort of patients with non-metastatic urothelial carcinoma of the upper urinary tract (UTUC). METHODS: Within the Surveillance, Epidemiology and End Results database (2004-2015), 6826 patients were identified. Conditional 5-year CSS estimates were assessed after event-free follow-up duration. Multivariable Cox regression (MCR) models predicted cancer-specific mortality (CSM) according to event-free follow-up length. RESULTS: Overall, 956 (14.0%) were T1 low grade(LG)N0 , 1305 (19.1%) T1 high grade(HG)N0 , 1215 (17.8%) T2 N0 , 2249 (32.9%) T3 N0 and 1101 (16.1%) T4 N0 /Tany N1-3 . From baseline, 93.4% to 94.2% in T1 LGN0 provided 5-year CSS and, respectively, 86.2% to 95.3% in T1 HGN0 , 77.5% to 87.8% in T2 N0 , 63.0% to 91.1% in T3 N0 , and 38.8% to 88.2% in T4 N0 /Tany N1-3 . In MCR models, relative to T1 LGN0 , T1 HGN0 (Hazard ratio [HR] 1.7), T2 N0 (HR 3.0), T3 N0 (HR: 5.2), and T4 N0 /Tany N1-3 (HR 11.9) were independent predictors of higher CSM. Conditional HRs decreased to levels equivalent to T1 LGN0 at 3 years vs 5 years of event-free survival for T1 HGN0 and all other groups, respectively. CONCLUSIONS: A direct relationship exists between event-free follow-up and survival probability after RNU. From a clinical perspective, such survival estimates may have particular importance during preoperative counseling.

Correlation of sex-determining region Y-box 30 with tumor characteristics and its prognostic value in breast cancer.

OBJECTIVE: Sex-determining region Y-box 30 (SOX30) suppresses progression of several cancers, whereas its role in breast cancer is unclear. Therefore, we aimed to determine the correlation of SOX30 with tumor characteristics and prognosis in breast cancer patients. METHODS: The tumor samples of 510 breast cancer patients who underwent resection were obtained, and SOX30 expression was analyzed by immunohistochemistry. Clinical characteristics, disease-free survival (DFS), and overall survival (OS) of breast cancer patients were recorded. RESULTS: There were 368 breast cancer patients in SOX30 low-expression group and 142 in SOX30 high-expression group. SOX30 was negatively correlated with tumor size (P = .010), tumor (T) stage (P < .001), node (N) stage (P = .001), and tumor, node, metastasis (TNM) stage (P < .001) in breast cancer patients. For prognosis, patients in SOX30 high-expression group had prolonged DFS (P = .011) and OS (P = .002); moreover, increased SOX30 grade (assessed by semi-quantitative scoring method assessment) was correlated with better DFS (P = .015) and OS (P = .014). Univariate Cox's regression analysis disclosed that SOX30 high expression was correlated with enhanced DFS (P = .012, hazard ratio (HR) = 0.582) and OS (P = .002, HR = 0.389); however, multivariate Cox's regression analysis revealed that SOX30 could not independently predict DFS (P = .224, HR = 0.766) or OS (P = .087, HR = 0.582) in breast cancer patients, indicating it might interact with other independent predictive factors (such as pathological differentiation, T stage, and N stage) to influence DFS and OS in breast cancer patients. CONCLUSION: Sex-determining region Y-box 30 is a potential prognostic biomarker in breast cancer, which might contribute to the better outcome of breast cancer patients.