Prognostic importance of DNA from human papillomavirus in patients with oral squamous cell carcinoma

Background: Survival of patients with oral squamous cell carcinoma (OSCC) is generally low, with the likelihood of locoregional recurrence or disease progression (LR/DP). Knowledge of prognostic factors for survival is key to achieving an understanding and increased survival. The present study aimed to identify prognostic factors for patients with OSCC, especially the presence of DNA from human papillomavirus (HPV). Material and Methods: Retrospective cohort study including 119 patients with OSCC treated at the National Cancer Institute in Mexico City (2009-2013). Clinical information was obtained from patient records including LR/DP. Formalin-fixed, paraffin-embedded tissues were obtained and used for detecting DNA from different types of HPV. Potential prognostic factors for Overall Survival (OS) were analyzed using the Cox proportional hazards model. Results: After model adjustment, factors associated with longer OS were a pre-treatment platelet count above 400,000/mm3 (HR=0.09, p=0.026) and response to primary treatment (HR=0.26, p=0.001). HPV DNA was present in 23 (19.3%) of the patients and importantly, type 16 found in 19 of them. Although survival of HPV-positive patients was longer, difference was not significant. However, among patients with LR/DP, HPV positivity was significantly associated with increased survival (HR=0.23, p=0.034). Importantly, survival was significantly different for HPV-positive patients with LR/DP > 6 months (HR=0.20, p=0.002), had higher absolute lymphocyte count at start of treatment (HR=0.50, p=0.028) or had local rescue treatment (HR=0.24, p=0.019). Conclusions: Although HPV positivity was not associated with a longer OS of OSCC patients, a better prognosis was significantly associated with HPV positivity and recurring or progressing disease, particularly with HPV type 16.(AU)

Transcriptome Analysis Identifies GATA3-AS1 as a Long Noncoding RNA Associated with Resistance to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients.

Breast cancer is one of the leading causes of mortality in women worldwide, and neoadjuvant chemotherapy has emerged as an option for the management of locally advanced breast cancer. Extensive efforts have been made to identify new molecular markers to predict the response to neoadjuvant chemotherapy. Transcripts that do not encode proteins, termed long noncoding RNAs (lncRNAs), have been shown to display abnormal expression profiles in different types of cancer, but their role as biomarkers in response to neoadjuvant chemotherapy has not been extensively studied. Herein, lncRNA expression was profiled using RNA sequencing in biopsies from patients who subsequently showed either response or no response to treatment. GATA3-AS1 was overexpressed in the nonresponder group and was the most stable feature when performing selection in multiple random forest models. GATA3-AS1 was experimentally validated by quantitative RT-PCR in an extended group of 68 patients. Expression analysis confirmed that GATA3-AS1 is overexpressed primarily in patients who were nonresponsive to neoadjuvant chemotherapy, with a sensitivity of 92.9% and a specificity of 75.0%. The statistical model was based on luminal B-like patients and adjusted by menopausal status and phenotype (odds ratio, 37.49; 95% CI, 6.74-208.42; P = 0.001); GATA3-AS1 was established as an independent predictor of response. Thus, lncRNA GATA3-AS1 is proposed as a potential predictive biomarker of nonresponse to neoadjuvant chemotherapy.

Stage I-III colon cancer patients with tumor deposits behave similarly to stage IV patients. Cross-section analysis of 392 patients.

BACKGROUND AND OBJECTIVES: Tumor deposits (TDs) are associated with adverse prognostic factors and decreased survival in colorectal cancer. However, controversy exists regarding their definition, evaluation, and staging categories. This study aimed to determine the survival and recurrence impact of the TD in colon adenocarcinomas; and to determine if TD patients behave similarly to stage IV patients. METHODS: Cross-section study from 392 patients with colon adenocarcinoma from 2005 to 2012. We performed survival analysis and further stratified patients considering TD patients as a "stage IV-TD" to demonstrate if they behave similarly than stage IV patients. RESULTS: From 392 patients, 204 (52%) were men, the mean age was 57.4 ± 13.9 years and 11.5% of cases had TD. In a multivariate analysis, TD failed to predict mortality and recurrence. Considering cases with TD as stage IV-TD, their mean survival was similar to stage IV patients (69.3 and 64.6 months, respectively) and different to those in stage III (110.5 months), II (135.7 months), and I (114.9 months) (P < 0.001). CONCLUSIONS: TD failed to predict mortality and recurrence. Patients with TD in stage I-III shows similar mortality than stage IV patients; then, we suggest putting them into a substage IV category instead of the N1c category.

Mesorectal Invasion Depth in Rectal Carcinoma Is Associated With Low Survival.

BACKGROUND: Most cases of rectal cancer (RC) in our institution are in pathologic stage T3. They are a heterogeneous group but have been classified in a single-stage category. We performed the present study to validate the prognostic significance of the mesorectal extension depth (MED) in T3 RC measured in millimeters beyond the muscularis propria plane. MATERIALS AND METHODS: We performed a retrospective analysis of 104 patients with T3 RC who had undergone curative surgery after a course of preoperative chemoradiotherapy at a tertiary referral cancer hospital. The patients were grouped by MED (T3a, < 1 mm; T3b, 1-5 mm; T3c > 5-10 mm; and T3d > 10 mm). The clinicopathologic data and disease-free survival were analyzed. RESULTS: The 5-year disease-free survival rate according to the T3 subclassification was 87.5% for those with T3a, 57.9% for T3b, 38.7% for T3c, and 40.3% for those with T3d tumors (P = .050). On univariate and multivariate analysis, the prognostic factors affecting survival were overall recurrence (hazard ratio [HR], 3.670; 95% confidence interval [CI], 1.710-7.837; P = .001), histologic grade (HR, 2.204; 95% CI, 1.156-4.199; P = .016), mesorectal invasion depth (HR, 1.885; 95% CI, 1.164-3.052; P = .010), and lymph node metastasis (HR, 1.211; 95% CI, 1.015-1.444; P = .033). CONCLUSION: MED is a significant prognostic factor in patients with T3 RC who have undergone neoadjuvant chemoradiotherapy, especially when the MED is > 5 mm. The MED could be as important as other clinicopathologic factors in predicting disease-specific survival.

Thyroid Transcription Factor-1 Expression in Adenocarcinomas of the Bile Duct.

BACKGROUND: The immunoreactivity of thyroid transcription factor-1 (TTF-1) is a very specific marker for lung and thyroid neoplasms; the expression of TTF-1 has also been demonstrated in extrapulmonary carcinomas. We examined the expression of TTF-1 in 15 intestinal-type adenocarcinomas of the extrahepatic bile duct. We then compared the expression to TTF-1 staining with other immunohistochemical markers including cytokeratin (CK) 7, CK20, caudal-type homeobox transcription factor 2 (CDX2), Napsin A, and MUC2. We additionally compared the clinicopathological prognostic factors with the TTF-1 expression status. RESULTS: Nuclear TTF-1 staining was detected in 2 cases (13.3%), and Napsin A was positive in the same 2 cases (13.3%). All cases were positive for CK20, CDX2, and MUC2; 5 cases were positive for CK7. There was no correlation between TTF-1 expression and the clinicopathological characteristics. CONCLUSIONS: To avoid potential pitfalls, TTF-1 should be interpreted in conjunction with the clinical setting, histology, and the results of markers such as CK7, CK20, Napsin A, and CDX2. This report is the first of TTF-1 positivity in adenocarcinomas from the extrahepatic biliary tract.

Un adecuado número de ganglios linfáticos puede ser obtenido en la mayoría de los especímenes quirúrgicos de resección radical de recto después de tratamiento neoadyuvante / An adequate lymph node retrieval is possible in almost all surgical specimens of rectal resection after neoadjuvant treatment

El propósito del estudio fue determinar si en pacientes con cáncer de recto (CR) posterior a tratamiento neoadyuvante (TNA) se puede obtener un adecuado número de ganglios linfáticos (GL) y si este correlaciona con la supervivencia. Setenta pacientes se dividieron en 2 grupos de acuerdo con si recibieron o no TNA. El grupo TNA se dicotomizó en < 12 GL y ≥ 12 GL. Los pacientes del grupo sin TNA mostraron mayor invasión vascular (33,3% vs. 14,3%) y perineural (19% vs. 4,1%). La media de GL del grupo TNA fue 15,7 + 7,1 vs. 27,28 + 14,9 (p = 0,0238) y se disecaron ≥ 12 GL en 74% vs. 90,5% (p = 0,0326). Los subgrupos con <12 y ≥ 12 GL no influyeron en el estadio N, estadio clínico ni supervivencia. La supervivencia media a 5 años del grupo TNA fue 82,3% vs. 76,9% (p = 0,465) (AU)

The aim of this study was to assess the possibility of obtaining an adequate number of lymph nodes (LN) from rectal cancer patients treated with neoadjuvant therapy (NAT) and to evaluate the correlation of LN with survival. 70 patients were divided into two groups: those who had received NAT and those who had not. The NAT group was further divided into those with < 12 LN and > 12 LN. The non-NAT group showed more lymph vascular invasion (33.3% vs. 14.3%) and perineural invasion (19% vs. 4.1%). Average LN in NAT group was 15.7 + 7.1 vs. 27.28 + 14.9 (p = 0.0238) and ≥ 12 LN were resected in 74% vs. 90.5% (p = 0.0326). The <12 and > 12 LN groups showed no difference in N stage, staging and survival. The 5-yr survival of NAT group was 82.3% v 76.9% (p = 0.465) (AU)

Frequency of high-grade prostatic intraepithelial neoplasia in Mexican population.

BACKGROUND: High-grade intraepithelial neoplasia (HGPIN) is the only lesion regarded as precursor of prostatic carcinoma, though its frequency is unknown in many countries. Here we studied the frequency of HGPIN in a population with high grade frequency of prostatic carcinoma. MATERIAL AND METHODS: A total of 486 cases of sextant prostatic biopsies performed from January 2001 to January 2006 were reviewed. These included 280 biopsies from patients belonging to an urban population, with medium or high socioeconomic status, from two hospitals in Mexico City. For comparison, 206 cases from the Regional Hospital of Tabasco located in the tropical zone of the country were included. This hospital receives patients from a rural population with low income and socioeconomic status. RESULTS: Of the total 486 cases, 162 (33.33%) cases were diagnosed as prostatic carcinoma and 319 (65.64%) as benign conditions. Only in five (1.03%) biopsies was HGPIN found. Three of these patients were from Mexico City, and two from the Regional Hospital of Tabasco. CONCLUSIONS: Even when our results were obtained only in three hospitals, they suggest that a low frequency of HGPIN on needle prostate biopsies does not necessarily mean a low frequency of prostatic carcinoma in the same population. The reason for such a disparity could be related to a reduced extension of HGPIN areas in the prostate gland. In populations with low frequency of HGPIN and high incidence of prostatic carcinoma, perhaps more biopsy cores should be obtained in order to minimize false negative results for premalignant lesions or early adenocarcinoma.