ABSTRACT
BACKGROUND AND AIMS: Ulcerative colitis (UC) patients have a greater risk of developing colorectal cancer through inflammation-dysplasia-carcinoma sequence of transformation. The histopathological diagnosis of dysplasia is therefore of critical clinical relevance, but dysplasia may be difficult to distinguish from inflammatory changes. METHODS: A proteomic pilot study on 5 UC colorectal dysplastic patients highlighted proteins differentially distributed between paired dysplastic, inflammatory and normal tissues. The best candidate marker was selected and immunohistochemistry confirmation was performed on AOM/DSS mouse model lesions, 37 UC dysplasia, 14 UC cancers, 23 longstanding UC, 35 sporadic conventional adenomas, 57 sporadic serrated lesions and 82 sporadic colorectal cancers. RESULTS: Differential proteomics found 11 proteins significantly more abundant in dysplasia compared to inflammation, including Solute carrier family 12 member 2 (SLC12A2) which was confidently identified with 8 specific peptides and was below the limit of quantitation in both inflammatory and normal colon. SLC12A2 immunohistochemical analysis confirmed the discrimination of preneoplastic and neoplastic lesions from inflammatory lesions in mice, UC and in sporadic contexts. A specific SLC12A2 staining pattern termed "loss of gradient" reached 89% sensitivity, 95% specificity and 92% accuracy for UC-dysplasia diagnosis together with an inter-observer agreement of 95.24% (multirater κfree of 0.90; IC95%: 0.78 - 1.00). Such discrimination could not be obtained by Ki67 staining. This specific pattern was also associated with sporadic colorectal adenomas and cancers. CONCLUSIONS: We found a specific SLC12A2 immunohistochemical staining pattern in precancerous and cancerous colonic UC-lesions which could be helpful for diagnosing dysplasia and cancer in UC and non-UC patients.
ABSTRACT
Pseudomyxoma peritonei (PMP) is a rare condition that refers to a clinical syndrome resulting from the accumulation of mucin in the peritoneal cavity. It results from the intraperitoneal rupture of a mucinous epithelial neoplasm which is classically appendiceal. The prognosis of a limited appendiceal tumor is favourable. Nevertheless, in the case of peritoneal dissemination, the prognosis could be different according to the histological type and therapeutic management. We report the case of a 71-year-old female patient who developed a pseudomyxoma peritonei originating from an appendiceal adenocarcinoma.
Le pseudomyxome péritonéal (PMP) est une condition rare qui se réfère à un syndrome clinique résultant d'une accumulation de mucine dans la cavité péritonéale. Il est secondaire à la rupture intrapéritonéale d'une néoplasie épithéliale mucineuse dont l'origine est classiquement appendiculaire. Le pronostic d'une tumeur appendiculaire limitée est favorable. Toutefois, en cas de dissémination péritonéale, il est variable selon le type histologique et la prise en charge thérapeutique. Nous rapportons le cas d'une patiente de 71 ans ayant développé un pseudomyxome péritonéal secondaire à un adénocarcinome appendiculaire.
Subject(s)
Ascites/etiology , Peritoneal Neoplasms/complications , Pseudomyxoma Peritonei/complications , Aged , Ascites/diagnosis , Ascites/surgery , Diagnosis, Differential , Female , Humans , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/surgery , Pseudomyxoma Peritonei/diagnosis , Pseudomyxoma Peritonei/surgeryABSTRACT
One promising avenue towards the development of more selective, better anticancer drugs consists in the targeted delivery of bioactive compounds to the tumor environment by means of binding molecules specific for tumor-associated biomarkers. Eligibility of such markers for therapeutic use implies ideally three criteria : (i) accessibility from the bloodstream, (ii) expression at sufficient level and (iii) no (or much lower) expression in normal tissues. Most current discovery strategies (such as biomarker searching into body fluids) provide no clue as to whether proteins of interest are accessible, in human tissues, to suitable high-affinity ligands, such as systemically delivered monoclonal antibodies. Innovative proteomic technologies are able to identify such accessible biomarkers and represent a key step in the clinical development of such target therapies.
