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A wide range of treatments is now available for nonmelanoma skin cancer (NMSC), including 5-fluorouracil, ingenol mebutate, imiquimod, diclofenac, photodynamic therapy, methotrexate, cetuximab, vismodegib, and radiotherapy. All are associated with high clinical and histologic response rates. However, some tumors do not respond due to resistance, which may be primary or acquired. Study of the resistance processes is a broad area of research that aims to increase our understanding of the nature of each tumor and the biologic features that make it resistant, as well as to facilitate the design of new therapies directed against these tumors. In this article we review resistance to the authorized topical treatments for NMSC., (Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Context and Objective: To analyze the influence of different alterations in human leukocyte antigen class I molecules (HLA I) in renal cell carcinoma, as well as in bladder and prostate cancer. We also study the correlation between HLA I expression and the progression of the disease and the response after immunotherapy protocols., Evidences Acquisition: It has been shown, experimentally, that the immune system can recognize and kill neoplastic cells. By analyzing the expression of HLA I molecules on the surface of cancer cells, we were able to study the tumor escape mechanisms against the immune system., Evidences Synthesis: Alteration or irreversible damage in HLA I molecules is used by the neoplastic cells to escape the immune system. The function of these molecules is to recognize endogenous peptides and present them to T cells of the immune system. There is a clear relationship between HLA I reversible alterations and success of therapy. Irreversible lesions also imply a lack of response to treatment. The immune system activation can reverse HLA I molecules expression in tumors with reversible lesions, whereas tumors with irreversible ones do not respond to such activation. Determine the type of altered HLA I molecules in tumors is of paramount importance when choosing the type of treatment to keep looking for therapeutic success. Those tumors with reversible lesions can be treated with traditional immunotherapy; however, tumour with irreversible alterations should follow alternative protocols, such as the use of viral vectors carrying the HLA genes to achieve damaged re-expression of the protein., Conclusion: From studies in urologic tumors, we can conclude that the HLA I molecules play a key role in these tumors escape to the immune system., (Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.)

Introduction: Colorectal cancer (CRC) can induce an anti-tumoral immune response mediated by T-lymphocytes, which express CD3., Objectives: To analyze the prognostic value of tissue expression of intraepithelial CD3 (CD3I) both overall and in the early tumoral stages., Methods: We revised 251 patients with resected CRC and favorable clinical course. CD3I expression was analyzed by immunohistochemistry. Multivariate analysis was used to analyze the variables independently associated with survival. We analyzed CD3I(+) expression in relation to survival and tumoral progression, both overall and in patients with pTNM(I-II) stage tumors. The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of CD3I expression were analyzed., Results: A total of 25.9% of patients with CRC were CD3I(+). After a mean follow-up of 74 months, CD3I(+) expression showed a favorable prognostic value for survival in the multivariate analysis (p=0.045). Survival curves and absence of tumoral progression were more favorable in CD3I(+) cases, both overall (p=0.009 and p=0.004, respectively), and in stages I-II (p=0.029 and p=0.015). The specificity and positive predictive value of CD3I(+) were as follows: Survival: overall: specificity =0.89; positive predictive value =0.91. Stage (I-II): specificity =0.94; positive predictive value =0.98. Absence of tumoral progression: overall: specificity=0.89; positive predictive value =0.88. Stage (I-II): specificity =0.92; positive predictive value =0.96., Conclusions: CD3I expression has an favorable independent prognostic value, with statistically significantly higher percentages of survival and absence of tumoral progression. This more favorable outcome is maintained in the less advanced stages (I-II). CD3I expression shows high specificity and positive predictive value., (Copyright © 2012 Elsevier España, S.L. and AEEH y AEG. All rights reserved.)

Introduction: Pre and post-operative oncological therapy in patients with breast cancer is determined, amongst other factors, by hormone receptor status and by c-erbB2 expression. The aim of this study is to determine the influence of neoadjuvant therapy on the expression of oestrogen receptor (OR), progesterone receptor (PR) and c-erbB2., Methods: Fifty-three patients with breast cancer diagnosed by tru-cut biopsy were studied. Patients with locally advanced carcinoma (20) had preoperative treatment. All patients underwent surgical resection. Expression of OR, PR and c-erbB2 in both the tru-cut biopsy and the gross specimen was compared., Results: We found significant differences in OR, PR expression in both biopsy and gross specimen, between the group of patients who underwent neoadjuvant treatment and the group without pre-surgical treatment. Changes in PR, OR and c-erbB2 status were found between the tru-cut biopsy and the gross specimen, in about 10 to 40% of the cases who received neoadjuvant therapy. These changes had no statistical significance.

Introduction: Although the association between benign neoplasias of the thymus and myasthenia gravis is well known, with greater predominance of squamous thymomas over other histological types, carcinoma of the thymus is only exceptionally associated with auto immune disorders., Case Reports: We present three patients with myasthenia gravis associated with carcinoma of the thymus. They were three men aged between 38 and 73 years. Clinical features of myasthenia were generalized in two cases and ocular only in the third. Antireceptor antibodies to acetylcholine and anti striped muscle antibodies were present in all three patients. Repetitive stimulation was abnormal in two of the three cases. On CAT of the thorax there was a tumour of the thymus with the radiological characteristics of a benign thymoma in two of the patients and data suggesting an invasive thymoma in the third. In all three cases the diagnosis of carcinoma of the thymus was made on the post operative histological findings., Conclusions: The association of carcinoma of the thymus with myasthenia gravis in our series of cases was probably due to chance. We consider that this association is exceptional since the histological characteristics of carcinoma of the thymus do not favour the development of auto immunity.

The current study deals with the setting up of a new tool that enables the benign versus the malignant nature of colorectal epithelium to be determined early and accurately. The objective is to determine a different biologic characteristic between normal and malignant colorectal tissue, which is the site and the level of expression of the T glycoepitope (Thomsen-Friedenreich antigen). It was characterized in a series of 62 colorectal samples, including 31 normal (without pathologic lesion) and 31 cancerous (mostly moderately or poorly differentiated) tissue sections. The glycoconjugate expression was demonstrated by lectin-histochemistry, using PNA lectin. The binding patterns of the lectin were determined in both columnar and goblet cells, from normal and malignant colorectal tissue. The results show that specific and different glycochemical staining patterns could be identified between benign and malignant epithelium. The data of the cytostructural localization were submitted to statistical analyses, which strongly suggested the association between the patterns of expression of the T antigen and the degree of the tissue differentiation. The methodology developed can be applied directly in routine diagnosis and it has an important prognostic value.

Objective: To review the paraneoplastic complications described affecting the peripheral nervous system., Development: Different types of tumors, especially secretory carcinomas and some lymphomas may affect the peripheral nerves, and this may often precede clinical signs of the tumor. Depending on the clinical features we may consider sensory neuropathies, motor neuropathies, senso-motor neuropathies, autonomic neuropathies, mononeuritis, and neuromyotonia. They may present in an isolated form or as part of a more generalized involvement of the nervous system., Conclusions: The presence of certain anti-Hu antibodies, which act against nerves or antibodies which attack the voltage-dependent potassium channels in a peripheral nervous system disorder make one suspect a paraneoplastic origin.

Objective: We have investigated the prevalence, signification and prognostic value of lymphocytic infiltration associated to differentiated thyroid carcinoma in our series of differentiated carcinoma of the thyroid., Methods: We studied the presence of lymphocytic infiltration in 223 patients effected of differentiated thyroid carcinoma, 138 of them were papillary carcinoma. The diagnostic was made with optic microscopy and we studied antithyroid antibodies in these patients. In survival analysis we studied all the variables of the patients and the event used as end point was death due to thyroid carcinoma, summarized in Kaplan-Meir curve and Cox method., Results: We found eight patients with differentiated thyroid carcinoma, six with papillary carcinoma, and lymphocytic thyroiditis and in three cases, antithyroid antibodies were present at low levels. We did not found any difference between the two groups and the survival rate was similar., Conclusions: These data support that in our series the prevalence of lymphocytic infiltration was low and probably without prognostic signification.

Sixteen axillary lymph nodes were incubated with sera from patients with mammary carcinoma. Using immunofluorescence staining sera recognized antigenic determinants on follicular dendritic cells (FDC) within the follicle centers. These results were confirmed with isolated and cultured FDC that were incubated with the same sera. All the results were negative with normal sera. We also found a cell population positively reacting with a monoclonal antibody against an estrogen receptor associated protein (ERAP) in subcapsular and cortical sinusae and germinal centers. Phenotype identification of ERAP+ cells indicated that they presented characteristics of macrophages and FDC respectively. Lymph nodes from other malignancies were negative for ERAP. These findings suggest that the tumoral antigen could be either the protein associated with the estrogen receptor or the receptor itself. The ERAP could be transported by the macrophages from the tumor to the regional lymph nodes where it could be processed and maintained during a long time by FDC, since it is known that these are the most efficient antigen presenting cells.

The relationship between nasopharyngeal carcinoma (NPC) and Epstein-Barr virus (EBV) has been already well established. Titulation of the antibodies IgG and IgA against EBV-related antigens has been proved reliable but always suitable having tested and age-matched control population. We present here the preliminary results from the 14 patients bearing NPC and 12 patients with other carcinoma of the head and neck and healthy donors.