Hematopoyesis Clonal de Potencial Indeterminado (HCPI): más allá de un modelo de campo de cancerización / Clonal hematopoiesis of indeterminate potential (CHIP): Beyond a model of field cancerization

Resumen La Hematopoyesis Clonal de Potencial Indeterminado (HCPI), más conocida como CHIP por sus siglas en inglés, se define como la expansión clonal de Células Madre Hematopoyéticas (CMHs) que albergan una o más mutaciones somáticas (en la mayoría de los casos una sola mutación) sin un cáncer hematológico subyacente ni evidencia morfológica definitiva de displasia, con una frecuencia alélica mayor al 2%. Los individuos con HCPI progresan a malignidad a una tasa de cerca del 0.5% a 1% por año, convirtiéndose así en un modelo de campo de cancerización. Sin embargo, sus implicaciones van más allá debido a que se ha encontrado asociación con enfermedades inflamatorias crónicas, como enfermedad cardiovascular ateroesclerótica, diabetes y enfermedades autoinmunes. Además, es considerado un factor predictivo en pacientes con cáncer hematolológico y no hematológico que reciben quimioterapia y radioterapia.

Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is the expansion of hematopoietic stem cells harboring one or more somatic mutations. These patients do not have underlying hematologic neoplasia, myelodysplasia, or dysplasia, but can progress to a malignant state at a rate of 0.5 to 1% per year. CHIP could be used as a model of field cancerization, since it has been associated with chronic inflammatory diseases, arteriosclerosis, diabetes, and autoimmune conditions. CHIP is also considered a predictive factor in hematological and non-hematological cancer patients receiving chemotherapy and radiotherapy.

Expression of Ki-67, Cyclin D1, P53, and P16 in patients with oral leukoplakia and leukoplakia cancerization with spicy diet in Chengdu / 华西口腔医学杂志

OBJECTIVES@#To investigate the expression of Ki-67, Cyclin D1, P53, and P16 in patients with oral leukoplakia (OLK) and OLK cancerization who have aspicy diet in Chengdu.@*METHODS@#Thirtypatients with OLK andspicy diet and 15 patients with OLK without spicy diet in Chengdu were divided into three groups: hyperplastic OLK (OLK-), OLK with mild to moderate dysplasia (OLK+), and severe dysplastic  OLK or oral squamous cell carcinoma (OSCC) transforming from OLK (OLK++/OSCC). The expression of Ki-67, Cyclin D1, P53, and P16 were detected by immunohistochemistry and statistically analyzed.@*RESULTS@#The expression of Ki-67 and P53 in patients with or without spicy diet in the OLK+and OLK++/OSCC groups were stronger than that of the OLK- group (@*CONCLUSIONS@#Spicy diet did not have an influence on the expression of Ki-67, Cyclin D1, P53, and P16 in patients with OLK and OSCC. The expression of Ki-67, Cyclin D1, and P53 increased with the development of OLK, whereas P16 showed opposite expression trend.

Expression of CHMP4A and TSPYL-2 in early esophageal cancer and their significance / 临床与实验病理学杂志

Purpose To investigate the role of CHMP4A and TSPYL-2 in early pathogenesis of esophageal cancer.Methods Through comparison of the four subtractive libraries,early esophageal squamous cell carcinoma genes CHMP4A and TSPYL-2 were chosen for further study.Through RT-PCR and immunohistochemistry methods,CHMP4A and TSPYL-2's expression was detected in esophageal squamous cell carcinoma tissue,cancerous tissue and normal esophageal mucosa.Results CHMP4A and TSPYL-2 expression between esophageal squamous cell carcinoma and normal esophageal epithelium tissue had significant differences (P ＜ 0.05),and the CHMP4A gene expression in esophageal mucosa,field cancerization areas,esophageal squamous cell carcinoma tissue increased,while TSPYL-2 gene expression in esophageal mucosa,field cancerization areas,esophageal squamous cell carcinoma tissue decreased,which were consistent with the protein expression of CHMP4A and TSPYL-2.Conclusion CHMP4A and TSPYL-2 genes are differentially expressed in esophageal squamous cell carcinoma,which can be used as alternative genetic markers for further research.

Epithelial tumor development and exploration on the relationship between matrix / 实用肿瘤学杂志

We have confirmed that many of the intraepithelial neoplasia confined to in situ may never be found in some patients ,such as breast ,prostate and lung lesions ,but few of these lesions progress to malignancy are unexplained .Studies demonstrate that many invasive neoplasia and its precancerous lesions with similar genes changes,which provide the necessary premise for the late tumor metastatic ,just like specific promoter mutations driving the cancer development ,but the current radical view is that the mutations of the genes are not the driver of cancer development ,rather the microenvironment of the cells inhibits or promotes the development of tumor .Gen-eral view is that the epithelial cells are changed before the cell matrix in the development of neoplasia ,but recent evidences show that the cell matrix is the first to change .This paper will focus on how matrix changes affect the epithelial tumor development ,and this will bring new breakthrough for controlling epithelial tumors .

Una puesta al día en el tratamiento de las queratosis actínicas / An update on the treatment of actinic keratosis

Las queratosis actínicas son una de las causas más frecuentes de consultas dermatológicas. Están consideradas como lesiones premalignas que pueden evolucionar a carcinoma espinocelular invasor. Constituyen un marcador de fotodaño y actualmente se consideran como modelo de cancerización de campo. Existen diversos tipos de tratamientos que se clasifican en terapias dirigidas a la remoción de la lesión (crioterapia y / o quirúrgicos) y terapias dirigidas al campo de cancerización que incluyen: inmunomoduladores tópicos (imiquimod y diclofenaco), agentes quimioterapéuticos (5-Fluorouracilo y retinoides), Ingenol mebutato, dermoabrasión, peelings químicos, láser, terapia fotodinámica y terapias combinadas entre otras. El principal objetivo de esta revisión es realizar una actualización de las terapias dirigidas al campo de cancerización de las queratosis actínicas con sus respectivas indicaciones, ventajas y desventajas.

Actinic keratosis are one of the most common causes of dermatological consultation. Considered as premalignant lesions that can progress to invasive squamous cell carcinoma. Constitute a marker of photodamage and actually considered as a model of field cancerization. There are several types of treatments classified as therapies targeting the removal of the lesion (cryotherapy and / or surgery) and targeted therapies of field cancerization that include topical immunomodulators (imiquimod and diclofenac), chemotherapeutic agents (5-fluorouracil, and retinoids), ingenol mebutate, dermabrasion, chemical peels, laser, photodynamic therapy and combination therapies among others. The main objective of this review is to update therapies of field cancerization for actinic keratosis with their respective indications, advantages and disadvantages.

Effects of folate deficiency with HPV16 infection on cervix cancerization / 中华流行病学杂志

Objective To investigate the relationship between folate in serum,red blood cell (RBC),cervix cancerization,as well as the interaction between folate deficiency and HPV16 infection in cervix cancerization.Methods 254 samples were selected from the patients who were newly pathologically diagnosed of having cervix inflammation (CI),low-grade cervical intraepithelial neoplasia (CIN Ⅰ),high-grade cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ) and cervical squamous cell carcinoma (SCC).PCR and microbiological assay were adopted to detect HPV infection and folate concentration.Results Rates of HPV16 infection increased with the severity of cervix cancerization (tend:x2=34.96,P＜0.001),while decreased with concentrations of serum and RBC folate (tend:x2=42.17,P＜0.001; tend:x2=31.39,P＜0.001).There was a positive correlation between serum and RBC folate (r=0.405,P＜0.001).Data from grouping analysis showed that OR and aOR of serum and RBC folate appeared a rising trend,with statistical significance in CIN Ⅱ/Ⅲand SCC,but did not show the same trend in CIN Ⅰ.Results from interaction analysis showed that serum folate deficiency had an additive interaction with HPV16 infection in CIN Ⅱ/Ⅲ and SCC,while RBC folate having an additive interaction with HPV16 infection in the whole process of cervix cancerization.Conclusion Both serum and RBC folate deficiency could increase the risk of cervix cancerization,and folate deficiency might have a synergic action with HPV 16 in this procession.

Cambios moleculares en los márgenes de resección en el carcinoma de células escamosas de cavidad oral / Molecular changes in the resections borders in squamous cell cancer of oral cavity

Evaluación molecular de márgenes de resección en pacientes con carcinoma de células escamosas de cavidad oral sometidos a cirugía. 16 pacientes con carcinoma escamoso de cavidad oral, en cualquiera de sus localizaciones, sin tratamientos previos, intervenidos quirúrgicamente en el 2011. La pieza operatoria fue procesada por anatomía patológica a través del método tradicional, realizándose cortes adicionales que incluían: tumor y 0,5 cm de margen no tumoral. Se realizó hematoxilina-eosina y complementó con inmunomarcaje para p53, PCNA, Ki-67, factor de crecimiento epidérmico y receptor de crecimiento endotelial vascular. De los 16 pacientes en estudio la mayoría eran del género masculino, la edad promedio fue cercana a los 60 años, la mayoría eran pacientes consumidores de tabaco y alcohol. La lengua fue la localización más frecuente y los tumores se encontraban en un estadio avanzado (estadio III y IV). Estudio molecular: todos los marcadores evaluados se encontraban positivos en los márgenes de resección en el 93,75% de los pacientes. Los marcadores de proliferación celular como el PCNA y Ki-67 así como el p-53 se encontraban positivos entre 1,5 cm a 2 cm del tumor con un marcaje intenso. Por el contrario, el factor de crecimiento epidérmico el receptor de crecimiento endotelial vascular se encontraban positivos hasta 1,5 cm pero con menor intensidad. En el cáncer oral podemos observar con frecuencia cambios moleculares en el tejido aparentemente sano que rodea el tumor hasta por lo menos 15 mm.

The molecular evaluation of resection margins in patients with squamous cell carcinoma of oral cavity who underwent surgery. Field of cancerization concept. We included 16 patients with oral cavity squamous cell carcinoma in any of their locations,without pre treatment, surgically treated in our hospital in the 2011 year. The surgical specimen was processed by the pathology department of our institution, through the traditional method, additional sectioned including the tumor and at least 0.5 cm margin non tumorigenic. Study was performed hematoxylin eosin and was supplemented with immunostaining for p53, PCNA, Ki-67, epidermal growth factor receptor and vascular endothelial growth factor receptor. The most important features of the 16 patients studied were: The majorities were male, the average age was around 60 years old; most of them were tobacco and alcohol consumers. The tongue was the most frequent location and most of the tumors were in an advanced stage (stage III y IV). In molecular evaluation all the markers were positive in the resection margins in 93.75% of all patients. The cell proliferation markers suchas PCNA and Ki-67 and the p-53 were positive 1.5 cm to2 cm tumor with intense staining. Conversely, epidermal receptor grow factors and vascular endothelial grow factor receptor were positive up to 1.5 cm but with less intensity. In oral cancer can often observe molecular changes in the apparently healthy tissue surrounding the tumor to at least 15 mm.

Significance of aberrant expression of DNA methyltransferase 1 in cervical cancerization tissue and cervical cancer cell lines / 肿瘤研究与临床

Objective To explore the effects of aberrant expression of DNA methyltransferase 1 (DNMT1) in cervical cancerization tissue and cervical cancer cells.Methods Cervical tissues were collected from 80 cases with a diagnosis of invasive cervix squamous cell carcinoma (SCC),53 cases with high-grade cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ),52 cases with low-grade cervical intraepithelial neoplasia (CIN Ⅰ)and 53 cases with normal cervix (NC).Meanwhile,Caski (HPV16-positive) and C33A (HPV-negative) cells selected from cervical cancer cell lines were cultured routinely in vitro.The expression of DNMT1 protein and mRNA were examined by Western blot analysis and real-time PCR (qRT-PCR) in the tissues and cells,respectively.Results The levels of DNMT1 protein were 1.33,1.84 and 2.28,and the Ct-ratios (DNMT1/β-actin) of DNMT1 mRNA were 1.27,1.27 and 1.26 in CIN Ⅰ,CIN Ⅱ/Ⅲand SCC group,respectively.Comparing with NC group,the expression of DNMT1 protein or mRNA was elevated in deficient cervical groups,with statistical significance (F =110.57,P ＜ 0.001,F =2.68,P =0.048).The expression levels of DNMT1 protein were increased steadily according to severity of the cervix lesions (x2tend =50.80,P ＜ 0.001),however,the expression of DNMT1 mRNA was not observed the same tendency (x2tend =3.63,P ＞ 0.05).The results from experiment in vitro showed that the levels of DNMT1 protein or mRNA were both higher in Caski cell than in C33A cell,especially for DNMT1 mRNA with significantly difference (t =7.134,P =0.002).Conclusion Aberrant expression of DNMT1 protein or mRNA could link with the risk of cervical cancerization by both transcriptional and posttranscriptional mechanisms.There would be a synergistic effect between overexpression of DNMT1 and HPV16 infection in the progression of cervix carcinogenesis.

Clinical analysis of 52 cases of carcinomatous change of breast intraductal papilloma / 肿瘤研究与临床

Objective To explore the diagnosis and treatment of cancerization relative to breast intraductal papilloma. Methods Clinical and pathological data of 52 patients with cancerous change of intraductal papilloma were studied retrospectively from January 1998 to December 2008. Results 39 of the 52 cases were diagnosed as malignance or suspected malignance by at least one of the preoperative imaging examinations such as ultrasonography, breast mammography or ductography. Cancer cells were found in 13 of the 46 patients who received fine needle aspiration. Frozen section established the malignance in 18 of the 39 cases. In a postoperative pathological report, 32 cases were cancerization of intraductal papilloma (carcinoma in situ) and 16 were cancerous change with microinvasion, only 4 patients with invasive carcinoma. All the patients received surgical management, 26 of the 52 cases were treated with modified radical mastectomy, 8 of them were performed with breast-conserving surgery (segmental resection plus axillary lymph node resection),7 cases underwent total mastectomy and 11 were just conducted with segmental resection. Only one people was found with axillary node metastasis among the 34 patients who received axillary lymph node dissection.Conclusion The correct preoperative diagnosis of the carcinomatous change of breast intraductal papilloma are always difficult and inconclusive, the frozen section may be helpful and the final diagnosis relied on the fully drawing materials of pathology after the operation. Treatment should be varied based on different pathological findings.

Diffusion weighted imaging diagnosis of cancerization nodules of liver cirrhosis / 中国医学影像技术

Objective To investigate the clinical value of diffusion weighted imaging (DWI) in diagnosis of atypical cancerization nodules (CNs) of liver cirrhosis. Methods Totally 34 patients with atypical CNs of liver cirrhosis confirmed pathologically underwent routine MR, dynamic enhancement, and DWI (b=0, 500, 1000 s/mm~2). The detection rate of CNs of liver cirrhosis between routine MR and DWI was compared. Results Totally 21 patients with 28 cancerization nodules were diagnosed with routine and dynamic enhancement MR, while 27 patients with 37 cancerization nodules were detected with DWI. Significant difference was found in the detection rate between routine scan and DWI (P=0.025). Conclusion DWI shows more advantage than routine and dynamic enhancement MR for detection of liver cirrhosis with atypical CNs.