A Novel Prognostic Biomarker Panel for Early-Stage Colon Carcinoma.

Molecular characterization of colorectal cancer has helped us understand better the biology of the disease. However, previous efforts have yet to provide significant clinical value in order to be integrated into clinical practice for patients with early-stage colon cancer (CC). The purpose of this study was to assess PD-L1, GLUT-1, e-cadherin, MUC2, CDX2, and microsatellite instability (dMMR) and to propose a risk-panel with prognostic capabilities. Biomarkers were immunohistochemically assessed through tissue microarrays in a cohort of 144 patients with stage II/III colon cancer. A biomarker panel consisting of PD-L1, GLUT-1, dMMR, and potentially CDX2 was constructed that divided patients into low, medium, and high risk of overall survival or disease-free survival (DFS) in equally sized groups. Compared with low-risk patients, medium-risk patients have almost twice the risk of death (HR = 2.10 (0.99-4.46), p = 0.054), while high-risk patients have almost four times the risk (HR = 3.79 (1.77-8.11), p = 0.001). The multivariate goodness of fit was 0.756 and was correlated with Kaplan-Meier curves (p = 0.002). Consistent results were found for DFS. This study provides a critical basis for the future development of an immunohistochemical assessment capable of discerning early-stage CC patients as a function of their prognosis. This tool may aid with treatment personalization in daily clinical practice and improve survival outcomes.

PD-L1 as a Prognostic Factor in Early-Stage Colon Carcinoma within the Immunohistochemical Molecular Subtype Classification.

BACKGROUND: There is a patent need to better characterize early-stage colorectal cancer (CRC) patients. PD-1 ligand (PD-L1) expression has been proposed as a prognostic factor but yields mixed results in different settings. The Consensus Molecular Subtype (CMS) classification has yet to be integrated into clinical practice. We sought to evaluate the prognostic value of PD-L1 expression overall and within CMS in early-stage colon cancer patients, in the hope of assisting treatment choice in this setting. METHODS: Tissue-microarrays were constructed from tumor samples of 162 stage II/III CRC patients. They underwent automatic immunohistochemical staining for PD-L1 and the proposed CMS panel. Primary endpoints were overall survival (OS) and disease-free survival (DFS). RESULTS: PD-L1 expression was significantly and independently associated with better prognosis (HR = 0.46 (0.26-0.82), p = 0.009) and was mostly seen in immune cells of the tumor-related stroma. CMS4 five-folds the risk of mortalitycompared with CMS1 (HR = 5.58 (1.36, 22.0), p = 0.034). In the subgroup CMS2/CMS3 analysis, PD-L1 expression significantly differentiated individuals with better OS (p = 0.004) and DFS (p < 0.001). CONCLUSIONS: Our study suggests that PD-L1 expression is an independent prognostic factor in patients with stage II/III colon cancer. Additionally, it successfully differentiates patients with better prognosis in the CMS2/CMS3 group and may prove significant for the clinical relevance of the CMS classification.

Usefulness of an immunohistochemical score in advanced pancreatic neuroendocrine tumors treated with CAPTEM or everolimus.

BACKGROUND: Pancreatic neuroendocrine tumors are rare neoplasms for which few predictive and/or prognostic biomarkers have been validated. Our previous work suggested the potential of the combined expression of N-myc downstream-regulated gen-1 (NDRG-1), O6-methylguanine DNA methyltransferase (MGMT) and Pleckstrin homology-like domain family A member 3 (PHLDA-3) as prognostic factors for relapse and survival. METHODS: In this new multicenter study we evaluated immunohistochemistry expression in 76 patients with advanced PanNET who were treated with capecitabine-temozolomide or everolimus. Based on the immunohistochemistry panel, an immunohistochemistry prognostic score (IPS) was developed. RESULTS: In patients treated with capecitabine and temozolomide, low IPS was an independent prognostic factor for progression-free-survival and overall-survival. Similar findings were observed with highest IPS for overall-survival in patients treated with everolimus. CONCLUSION: From our knowledge, it is the first time that a simple IPS could be useful to predict outcome for patients with metastatic pancreatic neuroendocrine tumors treated with everolimus or capecitabine and temozolomide.

Gene expression analyses determine two different subpopulations in KIT-negative GIST-like (KNGL) patients.

INTRODUCTION: There are limited findings available on KIT-negative GIST-like (KNGL) population. Also, KIT expression may be post-transcriptionally regulated by miRNA221 and miRNA222. Hence, the aim of this study is to characterize KNGL population, by differential gene expression, and to analyze miRNA221/222 expression and their prognostic value in KNGL patients. METHODS: KIT, PDGFRA, DOG1, IGF1R, MIR221 and MIR222 expression levels were determined by qRT-PCR. We also analyzed KIT and PDGFRA mutations, DOG1 expression, by immunohistochemistry, along with clinical and pathological data. Disease-free survival (DFS) and overall survival (OS) differences were calculated using Log-rank test. RESULTS: Hierarchical cluster analyses from gene expression data identified two groups: group I had KIT, DOG1 and PDGFRA overexpression and IGF1R underexpression and group II had overexpression of IGF1R and low expression of KIT, DOG1 and PDGFRA. Group II had a significant worse OS (p = 0.013) in all the series, and showed a tendency for worse OS (p = 0.11), when analyzed only the localized cases. MiRNA222 expression was significantly lower in a control subset of KIT-positive GIST (p < 0.001). OS was significantly worse in KNGL cases with higher expression of MIR221 (p = 0.028) or MIR222 (p = 0.014). CONCLUSIONS: We identified two distinct KNGL subsets, with a different prognostic value. Increased levels of miRNA221/222, which are associated with worse OS, could explain the absence of KIT protein expression of most KNGL tumors.

[Influence of Age in the Prevalence of High-Risk Human Papiloma Virus in Women with Pre-Neoplasic Cervical Lesions in Navarra, Spain]. / Influencia de la edad en la prevalencia de virus de papiloma humano de alto riesgo en mujeres con lesiones precursoras de cáncer de cuello uterino en la Comunidad Navarra.

OBJECTIVE: Cervical carcinoma (CC) is the second cause of death among women aged 15 and 44 in Spain. CC is linked to hig-risk human papillomavirus (HR-HPV) infection and its prevalence varies according age and geographical region. The awereness of the latter is essential for public health prevention efforts. The aim was to study the age related in HR-HPV genotypes in cytologies with squamous intraepithelial lesion (SIL). METHODS: From a total of 67,935 ginecologic cytologies over a four-year period, we selected cytologic specimens with SIL. We used the Cervista® test to detect HR-HPV DNA. Women were classified into two groups under 35 and over 35 years old. Proportions were estimated with confidence intervals at 95% (95% CI). RESULTS: HR-HPV prevalence was 59,7%; 64,6% in women under 35 years old. HR-HPV species alpha 9 type 16 (HR-HPV 16) and alpha 5 type 51 (HR-HPV 51) were the most prevalent (60,9% and 51,7%). High-grade squamous intraepithelial lesions (H-SIL) were twice as high in women under 35 years (6,5 vs. 3,7%). 88,8% of H-SIL was associated HR-HPV 16, which increases the probability of H-SIL against Low-grade squamous intraepithelial lesions (L-SIL) regardless of age. CONCLUSIONS: In our population HR-HPV 16 was associated to H-SIL whereas HR-HPV specie alpha 7 type 18 and HR-HPV 51 to L-SIL regardless of age. The high prevalence of HR-HPV 51 in Navrra´s population (51,7%), suggests that local vaccination programs be re-assessed.

El cáncer de cuello uterino (CCU)es la segunda causa de muerte en España en mujeres entre 15 y 44 años. Esta ligado íntimamente a la infección por el virus del papiloma humano de alto riesgo (VPH-AR). La prevalencia del VPH-AR incrementa según la gravedad de la lesión, grupo etario y región geográfica cuyo conocimiento es esencial para el desarrollo de estrategias de prevención. El objetivo fue determinar la influencia de la edad de las mujeres (menores o mayores de 35 años) en relación con la especie de VPH-AR presente y la lesión escamosa intraepitelial (LEI).

Influencia de la edad en la prevalencia de virus de papiloma humano de alto riesgo en mujeres con lesiones precursoras de cáncer de cuello uterino en la Comunidad Navarra / Influence of age in the prevalence of high-risk human papiloma virus in women with pre-neoplasic cervical lesions in Navarra, Spain

Fundamento: El cáncer de cuello uterino (CCU) es la segunda causa de muerte en España en mujeres entre 15 y 44 años. Esta ligado íntimamente a la infección por el virus del papiloma humano de alto riesgo (VPH-AR). La prevalencia del VPH-AR incrementa según la gravedad de la lesión, grupo etario y región geográfica cuyo conocimiento es esencial para el desarrollo de estrategias de prevención. El objetivo fue determinar la influencia de la edad de las mujeres (menores o mayores de 35 años) en relación con la especie de VPH-AR presente y la lesión escamosa intraepitelial (LEI). Material: Estudio observacional transversal de las citologías líquidas ginecológicas con LEI recibidas en el Hospital de Navarra entre 2010 y 2014 (67.935). A todas ellas se les realizó la detección del VPH-AR (Cervista®- Hologic). Las mujeres se clasificaron en menores de 35 e igual o mayores de 35 años. Se estimó la proporción e intervalo de confianza al 95% (IC95%). Resultados: La prevalencia de VPH-AR fue del 59,7%, el 64,6% en mujeres menores de 35 años. Las especies de VPH-AR alfa 9 del subtipo 16 (VPH-AR 16) y alfa 5 del subtipo 51 (VPH-AR 51) fueron los más frecuentes (60,9% y 51,7%). En las mujeres mayores de 35 años la prevalencia de lesiones escamosas de alto grado (H-SIL) fue 6,5 % y en las de menor edad 3,7%. El 88,8% de las H-SIL estaban asociadas a VPH-AR 16. La presencia de VPH-AR 16 quintuplica la probabilidad de H-SIL frente a LEI de bajo grado independientemente de la edad. Conclusiones: El VPH-AR 16 se asoció a H-SIL mientras que las especies de VPH-AR alfa 7 del subtipo 18 y VPH-AR 51 se asociaron a LEI de bajo grado independientemente de la edad. La alta prevalencia de VPH-AR en la Comunidad de Navarra puede ser relevante en la futura planificación de las estrategias de vacunación en nuestro entorno (AU)

Background: Cervical carcinoma (CC) is the second cause of death among women aged 15 and 44 in Spain. CC is linked to hig-risk human papillomavirus (HR-HPV) infection and its prevalence varies according age and geographical region. The awereness of the latter is essential for public health prevention efforts. The aim was to study the age related in HR-HPV genotypes in cytologies with squamous intraepithelial lesion (SIL). Methods: From a total of 67,935 ginecologic cytologies over a four-year period, we selected cytologic specimens with SIL. We used the Cervista® test to detect HR-HPV DNA. Women were classified into two groups under 35 and over 35 years old. Proportions were estimated with confidence intervals at 95% (95% CI). Results: HR-HPV prevalence was 59,7%; 64,6% in women under 35 years old. HR-HPV species alpha 9 type 16 (HR-HPV 16) and alpha 5 type 51 (HR-HPV 51) were the most prevalent (60,9% and 51,7%). High-grade squamous intraepithelial lesions (H-SIL) were twice as high in women under 35 years (6,5 vs. 3,7%). 88,8% of H-SIL was associated HR-HPV 16, which increases the probability of H-SIL against Low-grade squamous intraepithelial lesions (L-SIL) regardless of age. Conclusions: In our population HR-HPV 16 was associated to H-SIL whereas HR-HPV specie alpha 7 type 18 and HR-HPV 51 to L-SIL regardless of age. The high prevalence of HR-HPV 51 in Navarra´s population (51,7%), suggests that local vaccination programs be re-assessed (AU)

Cutaneous nodes in a patient with advanced papillary carcinoma of the thyroid.

Cutaneous metastasis from thyroid carcinoma is infrequent. Leukemia as a second malignancy after treatment of thyroid cancer is also rare. We present a patient with a relapsed thyroid carcinoma treated with thyroid ablation with I 131 and loco-regional radiotherapy, who consulted by global worsening, weight lost, and multiple cutaneous nodes. Our patient is unusual in that she showed multisystem involvement at the time of hospital admission, and the specific skin lesions were the first sign of her acute monocytic leukemia.

Doble adenoma corticosuprarrenal presencia de cuerpos de espironolactona / Double cortical adenoma with spironolactone

Los adenomas productores de aldosterona (síndrome deConn) son responsables de la mayoría de los casos de hiperaldosteronismoprimario. Se trata de tumores benignos depequeño tamaño, generalmente menores de 2 cm, localizadosen la corteza suprarrenal, bien delimitados y casi siempreúnicos. La presencia de dobles adenomas ipsilaterales esexcepcional, ocurre aproximadamente en el 8% de los adenomassuprarrenales.Presentamos el caso de una mujer de 59 años hipertensa,refractaria al tratamiento médico los últimos años a laque se descubre un tumor suprarrenal funcionante, secretorde aldosterona. Se realiza suprarrenalectomía laparoscópicay el estudio histológico de la pieza muestra la presencia dedos adenomas corticales. El mayor de ellos se encuentraconstituido por células fasciculares y el menor por célulashíbridas y glomerulosas. Además este último recoge otrohecho poco frecuente, aparecen inclusiones eosinófilas citoplasmáticasque corresponden a cuerpos de espironolactona.Se trata de estructuras multilaminares rodeadas de unhalo claro que miden entre 2 y 12 μm, están relacionadascon el uso de este fármaco pero no con la dosis ni la duracióndel tratamiento.Es la primera vez que se describe en la literatura la asociaciónde adenomas múltiples y la presencia de cuerpos deespironolactona, según la revisión bibliográfica realizada

Primary aldosteronism is due to an aldosterone-producingadenoma (Conn´s syndrome). This benign tumor isusually small, less than 2 cm diameter, sharply demarcatedand generally solitary. Only in a small percentage of cases(8%) unilateral double adenomas have been reported.A 59-year-old woman with a past medical history ofarterial hypertension presented no response to her antihypertensivemedication. An aldosterone secreting adrenocorticaltumor was found. After laparoscopic adrenalectomy,microscopical examination revealed the presence of twocortical adenomas. In the biggest tumor the most commoncellular population was fasciculata cells while in the smallone, we could found hybrid and glomerulosa cells. In thelatter spironolactone bodies were also found. These bodiesare normally found while the patient is taking spironolactonebut with no apparent correlation to dosage or duration oftreatment was reported.According to our literature review this is the first timethat the association of double cortical adenoma with spironolactonebodies is reported

[Prostate leiomiosarcoma. Report of three cases]. / Leiomiosarcoma de próstata, aportación de tres casos.

OBJECTIVE: Leiomyosarcoma of the prostate is an uncommon neoplasm with a poor prognosis. We review the three cases of leiomyosarcoma of the prostate observed in our hospital in the last twenty years and studied their clinical follow-up, METHODS: We have found three cases and we have studied their clinical follow-up, immunohistochemical profile and ultrastructural features. RESULTS: In all cases tumor cells were positive for vimentin and also for either desmin or actin. Two cases were considered grade III sarcomas, with an aggressive course even with treatment, they died 5 and 24 months later, respectively. The third case, was considered grade II and is still alive, 60 months after diagnosis, without evidence of disease. CONCLUSIONS: Leiomyosarcoma of the prostate is an uncommon neoplasm that accounts for less than 0.1% of prostate tumors. We found no prognostic factors for predicting prolonged survival although complete resection and low mitotic activity may be predictive.

Leiomiosarcoma de próstata, aportación de tres casos / Prostate leiomiosarcoma. Report of three cases

OBJETIVO: El leiomiosarcoma de próstata esun tumor muy poco frecuente cuya supervivencia a mediolargoplazo es baja. Hemos revisado los casos de esta patologíarecogidos en nuestro centro durante los últimos veinteaños.MÉTODO: Se han encontrado tres casos de leiomiosarcomade próstata y se ha estudiado su evolución clínica, grado histológico,perfil inmunohistoquímico y rasgos ultraestructurales.RESULTADOS: Todos los casos compartían la positividad paravimentina y actina o desmina. Dos casos fueron consideradossarcomas de grado III y siguieron un curso clínico agresivopese al tratamiento, falleciendo a los 5 y 24 meses respectivamente.El tercer caso, considerado un leiomiosarcoma degrado II permanece libre de enfermedad a los 60 meses deldiagnóstico sin tratamiento neoadyuvante.CONCLUSIONES: El leiomiosarcoma de próstata es untumor infrecuente que supone menos del 0,1% de las neoplasiasprostáticas. No existen factores pronósticos claros aunquela resección completa del mismo y el bajo grado histológicopueden ser predictivos

OBJETIVE: Leiomyosarcoma of the prostate isan uncommon neoplasm with a poor prognosis. We reviewthe three cases of leiomyosarcoma of the prostate observed inour hospital in the last twenty years and studied their clinicalfollow-up,METHODS: We have found trhee cases and we have studiedtheir clinical follow-up, immunohistochemical profile and ultrastructuralfeatures.Results: In all cases tumor cells were positive for vimentin andalso for either desmin or actin. Two cases were consideredgrade III sarcomas, with an aggressive course even with treatment,they died 5 and 24 months later, respectively. Thethird case, was considered grade II and is still alive, 60months after diagnosis, without evidence of disease.CONCLUSIONS: Leiomyosarcoma of the prostate is anuncommon neoplasm that accounts for less than 0.1% of prostatetumors. We found no prognostic factors for predicting prolongedsurvival although complete resection and low mitoticactivity may be predictive

Liposarcoma de cordón espermático: criterios de diagnóstico diferencial y tratamiento / Liposarcoma of the spermatic cord : Differential diagnosis and treatment

OBJETIVO: Describimos el caso de un liposarcoma de cordón espermático en un hombre joven, destacando los problemas de diagnóstico diferencial clínico e histopatológico.MÉTODO/RESULTADOS: Se le extirpó una tumoración de 8 x 7 cms. El diagnóstico patológico fue de liposarcoma bien diferenciado con áreas mixoides. En un segundo tiempo se realizó una orquiectomía radical izquierda. Actualmente el paciente se encuentra bien, sin recidivas ni metástasis.CONCLUSIONES: Los liposarcomas paratesticulares son tumores raros, lo que dificulta establecer pautas de tratamiento, pronóstico y diagnóstico diferencial. El diagnóstico pre-operatorio es difícil, si bien la ecografía y TAC pueden ser de gran ayuda. Al igual que en los liposarcomas de otras localizaciones es de valor pronóstico el tipo y grado histológico del tumor. El tratamiento de elección es la orquiectomía radical inguinal. (AU)