RESUMO
PURPOSE: The mechanisms of the progression of Barrett's oesophagus (BO) to oesophageal adenocarcinoma (OA) are poorly understood. The frequency of the 4977bp deletion in mitochondrial DNA (mtDNA) was investigated in specimens ranging from normal oesophageal tissue to OA in order to investigate whether this deletion represents a useful biomarker of disease progression. METHODS: The presence of the 4977bp deletion was screened by PCR amplification from 70 specimens in total. RESULTS: The frequency of specimens with the 4977bp deletion increased in relation to the degree of dysplasia (8.3% in normal squamous epithelium; 15.4% in BO; 40% in low grade dysplasia (LGD); 69.2% in high-grade dysplasia and 90% in para-tumoural tissue). However, the frequency of the deletion reduced sharply in OA specimens (16.7%; p<0.001). CONCLUSION: The mtDNA 4977bp deletion may be useful as a biomarker to detect the severity of dysplasia but not the presence of OA.
Assuntos
Esôfago de Barrett/genética , DNA Mitocondrial/genética , Neoplasias Esofágicas/genética , Deleção de Genes , Lesões Pré-Cancerosas/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Esôfago de Barrett/patologia , DNA de Neoplasias/genética , Progressão da Doença , Neoplasias Esofágicas/patologia , Humanos , Lesões Pré-Cancerosas/patologiaRESUMO
We report an unusual case of pravastatin-induced colitis in an 80-year old lady. Onset of symptoms was noted within 48 h of starting the medication. Colonoscopy revealed diffuse ulceration throughout the colon with relative sparing of the rectum, with the biopsies showing ulceration and inflammation. The patient received a short course of steroid therapy and 5 months after stopping pravastatin, there was complete macroscopic and microscopic resolution of the colonic lesions. Drug interaction of pravastatin with amitryptiline could have resulted in this uncommon complication.
Assuntos
Colite/induzido quimicamente , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Pravastatina/efeitos adversos , Idoso de 80 Anos ou mais , Colite/diagnóstico , Colite/patologia , Colonoscopia , Feminino , HumanosRESUMO
It is unclear whether and how cyclin D1 and/or p21(WAF1/CIP1) dysregulation contribute to ulcerative colitis (UC)-related inflammation and colorectal carcinogenesis. Cases of quiescent UC (QUC; n = 15), active UC (AUC; n = 23), UC-related dysplasia (n = 35) and UC-related colorectal adenocarcinomas (CRCs; n = 11) were studied with cyclin D1 and p21(WAF1/CIP1) immunohistochemistry. The CRCs were also studied with beta-catenin, bcl2, and p53 immunohistochemistry, p53 and k-ras mutation analyses, and cyclin D1 gene fluorescence in situ hybridization. QUC showed cyclin D1 (negative/weak staining) and p21(WAF1/CIP1) (surface epithelial and upper-third crypt staining) expression similar to that of normal colorectum. Moderate or strong cyclin D1 immunostaining was seen in 9% of AUC cases, 40% of dysplasia cases, and 36% of UC-related CRCs. Although these carcinomas showed neither cyclin D1 gene amplification nor any association between k-ras mutation and cyclin D1 overexpression, the latter was closely related to nuclear beta-catenin expression. Increased lower-third crypt p21(WAF1/CIP1) staining was seen in 57% of AUC cases; decreased upper-third crypt p21(WAF1/CIP1) staining, in 23% of dysplasia cases; and absent or weak p21(WAF1/CIP1) staining, in 55% of UC-related CRCs. The latter change was always associated with p53 mutation but could not be related to p53 or bcl2 expression. In conclusion, AUC shows up-regulated cyclin D1 and p21(WAF1/CIP1) expression. Cyclin D1 up-regulation and p21(WAF1/CIP1) down-regulation occur early in UC-related carcinogenesis. Cyclin D1 up-regulation is less common in UC-related CRCs than in sporadic CRCs, and is related to beta-catenin nuclear signaling. p21(WAF1/CIP1) down-regulation is seen at an equal or higher frequency among UC-related CRCs compared with sporadic CRCs and is attributable to p53 mutation.
