Purpose: As an approach to evaluate the expression pattern and status of activation of signaling pathways in clinical specimens from
head and neck squamous cell carcinoma (HNSCC) patients, we ...established the Head and Neck Cancer Tissue Array Initiative, an
international consortium aimed at developing a high-density HNSCC tissue microarray, with a high representation of oral squamous
cell carcinoma.
Experimental Design: These tissue arrays were constructed by acquiring cylindrical biopsies from multiple individual tumor tissues and transferring
them into tissue microarray blocks. From a total of 1,300 cases, 547 cores, including controls, were selected and used to
build the array.
Results: Emerging information by the use of phosphospecific antibodies detecting the activated state of signaling molecules indicates
that the Akt-mammalian target of rapamycin (mTOR) pathway is frequently activated in HNSCC, but independently from the activation
of epidermal growth factor receptor or the detection of mutant p53. Indeed, we identified a large group of tissue samples
displaying active Akt and mTOR in the absence of epidermal growth factor receptor activation. Furthermore, we have also identified
a small subgroup of patients in which the mTOR pathway is activated but not Akt, suggesting the existence of an Akt-independent
signaling route stimulating mTOR.
Conclusions: These findings provide important information about the nature of the dysregulated signaling networks in HNSCC and may also
provide the rationale for the future development of novel mechanism-based therapies for HNSCC patients.
Background
Cervical cancer (CC) is a global problem; it is among the five leading causes of cancer death in women. Several studies have examined the association between age and disease prognosis; ...however, controversy still exists. The objective of the present study is to determine if age at diagnosis has an impact on overall survival (OS) and disease‐free survival (DFS).
Materials and Methods
Retrospective cohort of 2,982 patients with CC treated at the National Cancer Institute of Mexico from 2005 to 2015. We collected demographic, clinical, and treatment data, as well as current status, of 2 groups: women under and over 40 years of age. We calculated OS and DFS rates with Kaplan‐Meier estimates. Cox proportional hazards modeling was used to determine risks.
Results
The median follow‐up time was 26.5 months (percentile P25–P75, 11–60.23). When comparing DFS, OS, stage, and histologic subtype between young patients <40 and adult patients >40, we did not observe any difference. We found that in both groups, locally advanced and advanced stage, neuroendocrine subtype, hydronephrosis, and positive inguinal lymph nodes increased the risks of death and recurrence. Having been pregnant was identified as protective factor in DFS (hazard ratio, 0.54; 95% confidence interval, 0.04–0.71).
Conclusion
We corroborated that age at diagnosis is not a prognostic factor for decreased or increased OS or DFS, and in both groups, the stage, histologic subtype, hydronephrosis, and node involvement were identified as factors adverse to OS and DFS, and pregnancy history was a protective factor in DFS.
Implications for Practice
The present study directly affects everyday clinical practice because it allows us to focus on the most relevant prognostic factors in patients with cervical cancer. When planning treatment and follow‐up, clinicians should focus on stage at diagnosis, histologic subtype, hydronephrosis, and distant metastasis instead of patients’ age. They should also be aware of any previous pregnancies and poor response, or nonresponse, to treatment, which results in disease progression and persistence. Paying attention to these factors affecting overall survival and disease‐free survival will help treat patients better and increase their chances of survival and improve their quality of life.
Cervical cancer is among the five leading causes of cancer morbimortality in women. This article focuses on age at diagnosis and the related effect on overall and disease‐free survival in this patient population.
Altered expression of microRNAs contributes to the heterogeneous biological behavior of human malignancies and it may correlate with the clinical pathological features of patients. The let-7 microRNA ...family is frequently downregulated in human cancers and its aberrant expression may be a useful marker for prediction of the clinical response to therapy in patients. In the present study, we analyzed the expression of three members of the let-7 family (let-7a-3p, let-7d-3p and let-7f), which remains largely uncharacterized in ovarian cancer tissues. We also investigated the function of let-7d-3p in the apoptosis and sensitization to chemotherapy in ovarian cancer cells. Our data from stem-loop quantitative RT-PCR showed that expression of let-7a-3p and let-7d-3p, but not let-7f, was significantly (P<0.04) upregulated in ovarian tumors relative to that noted in normal ovarian tissues. Markedly, an increased expression of let‑7d-3p (also known as let-7d-3*) was associated with positive response to carboplatin/paclitaxel treatment in ovarian cancer patients. To investigate the biological relevance of let‑7d-3p, we knocked down its expression in SKOV-3 ovarian cancer cell line using antagomiRs. Loss of function analysis showed that inhibition of let-7d-3p significantly (P<0.05) impaired cell proliferation and activated apoptosis. In contrast, scratch/wound healing and Transwell chamber assays showed that migration and invasion abilities were not affected in the let-7d-3p-deficient SKOV-3 cancer cells. Notably, Annexin V assays showed a significant (P<0.05) increase in cell death of cancer cells treated with the let-7d-3p inhibitor plus carboplatin indicating a synergistic effect of the drug with antagomiR therapy. Gene ontology classification of predicted targets of let-7d-3p identified a number of genes involved in cellular pathways associated with therapy resistance such as ABC transporters, HIF-1, RAS and ErbB signaling. In summary, our findings showed that inhibition of let-7d-3 activates apoptosis and that its upregulation is associated with a positive response of ovarian cancer patients to carboplatin/paclitaxel chemotherapy.
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.
Background
Mutations on KIT and downstream genes of MAPK pathway that overstimulate cellular proliferation have been associated with primary oral and sinonasal melanomas (POSNM), but there is limited ...information that allows the use of personalized therapy. Thus, the aim of the present study was to determine a possible association between the C‐KIT immunohistochemical expression with the presence of somatic driver mutations in NRAS, BRAF, KIT, MITF and PTEN on POSNM.
Methods
A retrospective study included 62 tumour samples of an oncological reference centre in Mexico City (17‐year period). Immunohistochemistry stain of C‐KIT was carried out. Genomic DNA was obtained and used to assess hotspot mutations of KIT, NRAS, BRAF, MITF and PTEN through qPCR. Chi‐square, Fisher's exact and the Mann‐Whitney U tests were applied when necessary. The significance was set at P < 0.05.
Results
Sixty‐two cases were included, 74% were positive for C‐KIT immunoexpression, all exhibited moderate/strong intensity. Ten (16.1%) samples harboured at least one mutation, 6.4% and 6.6% for NRASQ61R and BRAFV600E, respectively, followed by KITK624E (3.2%). No KITL576P, MITF or PTEN mutations were identified. No significant correlation was observed between mutations and immunostaining (rs = −0.057, P = 0.765).
Conclusions
Regardless of the high immunoexpression of C‐KIT, there was no association with the MAPK mutations among POSNM samples. Thus, C‐KIT immunohistochemistry is not a reliable tool to detect POSNM candidates for biological therapy.
Background
Factors associated with the time to surgery (TTS) and survival in colon cancer (CC) have not been well studied. Our aim was to find if the TTS has changed in our institution over time and ...to determine if it influences the survival.
Methods
Retrospective cross‐section study of 266 CC analyzed between two periods, and according to the quartiles of TTS, we performed a survival analysis.
Results
The median age was 57 years; there was no predominance of sex, and about half of the patients were in stage III. The median TTS was 38 days, and 75% of the cases were operated before 60 days. The median TTS for 2005 to 2010 was 36 days, while for 2011 to 2015 was 41 days (P = 0.107). The survival was not statistically different between cases (1) operated with a delayed TTS or not, (2) operated in four cut‐off points of TTS, (3) two different periods of attention, and (4) according to the clinical stage.
Conclusion
We did not find an association between the TTS with low survival. TTS has increased in the last period so we must work to make the diagnostic process more efficient in our patients to meet international quality standards.
Neoadjuvant chemotherapy aims to improve the outcome of breast cancer patients, but only few would benefit from this treatment. Pathological complete response has been proposed as a surrogate marker ...for the prediction of long-term clinical benefits; however, 50%–85% patients have an unfavorable pathological complete response to chemotherapy. MicroRNAs are known biomarkers of breast cancer progression; nevertheless, their potential to identify patients with pathological complete response remains poorly understood. Here, we investigated whether a microRNA profile could be associated with pathological complete response in triple-negative breast cancer patients receiving 5-fluorouracil, adriamycin, cyclophosphamide–cisplatin/paclitaxel as a novel neoadjuvant chemotherapy. In the discovery cohort, the expression of 754 microRNAs was examined in tumors from 10 triple-negative breast cancer patients who achieved pathological complete response and 8 without pathological complete response using TaqMan Low-Density Arrays. Unsupervised hierarchical cluster analysis identified 11 microRNAs with significant differences between responder and no-responder patients (fold change ≥ 1.5; p < 0.05). The differential expression of miR-30a, miR-9-3p, miR-770, and miR-143-5p was validated in an independent group of 17 patients with or without pathological complete response. Moreover, Kaplan–Meier analysis showed that expression of these four microRNAs was associated with an increased disease-free survival. Gene ontology classification of predicted microRNA targets indicated that numerous genes are involved in pathways related to chemoresistance, such as vascular endothelial growth factor, focal adhesion kinase, WNT, ERbB, phosphoinositide 3-kinase, and AKT signaling. In summary, we identified a novel microRNA expression signature associated with pathological complete response in breast cancer. We propose that the four validated microRNAs could be used as molecular biomarkers of clinical response in triple-negative breast cancer patients with pathological complete response to neoadjuvant therapy.
Background
The current study was performed to identify factors that are present at the time of breast cancer (BC) diagnosis that are associated with a higher rate of central nervous system metastasis ...(CNSm).
Methods
The authors analyzed a database of patients with a confirmed diagnosis of BC who were referred for a neuro‐oncology consultation at the National Cancer Institute in Mexico City, Mexico, from June 2009 to June 2017. Information was collected prospectively and included demographic, pathologic, and clinical data at the time of diagnosis of BC. Bivariate and multivariate logistic regression models were built to estimate the associations between the development of CNSm and the time after BC diagnosis.
Results
Among 970 patients with BC, 263 (27%) were diagnosed with CNSm. The median time from BC diagnosis to the development of CNSm was 33 months (interquartile range, 15‐76 months). After multivariate analysis, age <50 years at the time of BC diagnosis (odds ratio OR, 2.5; 95% confidence interval 95% CI, 1.8‐3.5 P < .0001), human epidermal growth factor receptor 2 (HER2)–positive status (HER2+) (OR, 3.6; 95% CI, 2.1‐6.1 P < .0001), luminal B/HER2+ subtype (OR, 3.1; 95% CI, 1.9‐5.3 P < .001), triple‐negative subtype(OR, 2.4; 95% CI, 1.5‐4 P = .001), and Karnofsky performance status ≤70 (OR, 6.6; 95% CI, 4.5‐9.6 P < .0001) were associated with a higher frequency of CNSm. Brain parenchyma was the most common site of CNSm. The median overall survival after a diagnosis of CNSm was 12.2 months (95% CI, 9.3‐15.1 months).
Conclusions
CNSm is not uncommon among patients with BC, particularly in those with neurologic symptoms who require neuro‐oncology evaluation and are aged <50 years at the time of diagnosis, have HER2+ or triple‐negative subtypes, have a poor Karnofsky performance status, and/or have ≥2 non‐CNS metastases.
Risk factors for central nervous system metastasis might be established at the time of breast cancer diagnosis in neuro‐oncology patients. The current study identifies the following factors as being associated with a higher risk: age, breast cancer subtype, and Karnofsky performance status.
•SARS-CoV-2 positivity rate in hospital Non-Covid in México was 9.6%.•Men, administrative staff and employees who had relatives also working in the same hospital had higher risk of infection.•Active ...surveillance help to detect a significant number of asymptomatic infections, is necessary to reinforce preventive measures in non-medical staff to prevent nosocomial transmission.
Healthcare workers are at increased risk of SARS-CoV-2 infection. The positivity rates in hospitals that do not receive patients with COVID-19, such as the National Cancer Institute (INCan) in Mexico, and the associated factors are unknown.
To assess the incidence and factors associated with SARS-CoV-2 infection in health workers at INCan.
A cohort study of 531 workers who were followed for 6 months. RT-PCR analysis of saliva and nasopharyngeal swab samples were used in the baseline and to confirm cases during follow-up The incidence rate ratio was calculated according to the measured characteristics and the associated factors were calculated using logistic regression models.
Out of 531 workers, 9.6% tested positive for SARS-CoV-2, Being male (RR: 2.07, 95% CI: 1.1-3.8, P = .02), performing administrative tasks (RR: 1.99, 95% CI: 1.0-3.9, P = .04), and having relatives also working at INCan (RR: 3.7, 95% CI: 1.4-9.5, P < .01) were associated with higher positivity rates.
Incidence of positive cases in health workers were similar to that reported in non-COVID hospitals from other countries.
Even though active surveillance helped to detect a significant number of asymptomatic infections, it is still necessary to reinforce preventive measures in non-medical staff to prevent nosocomial transmission.
To describe access to complete treatment in women with cervical cancer and state-sponsored insurance versus no insurance. We conducted a retrospective observational study. The source population ...consisted of women treated for cervical cancer from January 2000 to December 2015 in a tertiary care hospital. We included 411 women with state-sponsored insurance and 400 without insurance. We defined access to cervical cancer treatment as complete treatment (according NCCN/ESMO (National Comprehensive Cancer Network/European Society for Medical Oncology) standards) and timely initiation of treatment (less than 4 weeks). Clinical and sociodemographic characteristics were described and analyzed with logistic regression using complete treatment as the main outcome. A total of 811 subjects were included, the median age was 46 (IQR (Interquartile range) 42-50) years. Most of them were married (36.1%), unemployed (50.4%), and had completed primary school (44.0%). The most common clinical stages at diagnosis were II (38.2%) and III (24.7%). In the adjusted regression model, being married (OR (odds ratio): 4.3, 95% CI (confidence interval): 1.74-10.61) and having paid employment (OR: 2.79, 95% CI: 1.59-4.90) or state-sponsored insurance (OR: 1.54, 95% CI: 1.04-2.26) were positively associated with the possibility of having a complete treatment. Women with insurance were likely to be younger and receive timely treatment compared with uninsured women. Complete treatment was associated to insurance status and advanced stages of cervical cancer. State-sponsored insurance improves access to complete treatment. Government policies are needed to avoid social and economic inequity and provide better management of cervical cancer in our country.
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