Abstract Two Italian patients with the initial clinical diagnosis of Rothmund-Thomson syndrome were negative for RECQL4 mutations but showed in peripheral blood cells a spontaneous chromosomal instability significantly higher than controls. Revisiting after time their clinical phenotype, the suggestive matching with the autosomal dominant syndrome Poikiloderma, Hereditary Fibrosing with Tendon Contracture, Myopathy and Pulmonary fibrosis (POIKTMP) was confirmed by identification of the c.1879A>G (p.Arg627Gly) alteration in FAM111B. We compare the overall clinical signs of our patients with those of reported carriers of the same mutation and present the up-to-date mutational repertoire of FAM111B and the related phenotypic spectrum. Our snapshot highlights the age-dependent clinical expressivity of POIKTMP and the need to follow-up patients to monitor the multi-tissue impairment caused by FAM111B alterations. We link our chromosomal instability data to the role of FAM111B in cancer predisposition, pointed out by its implication in DNA-repair pathways and the outcome of pancreatic cancer in 2 out of 17 adult POIKTMP patients. The chromosomal instability herein highlighted well connects POIKTMP to cancer-predisposing syndromes, such as Rothmund-Thomson which represents the first hereditary poikiloderma entering in differential diagnosis with POIKTMP.

BACKGROUND: In this review, we focus our discussion on one class of carcinoembryonic antigen-related cell adhesion molecules, Carcinoembryonic antigen-related cell adhesion molecules 1 (CEACAM1). This has been observed in several malignant transformations to be subjected to complex mechanisms of modulation and dysregulation. AIMS: Restoration of CEACAM1 expression in tumor cell lines often abolishes their oncogenicity in vivo, and therefore, this adhesion molecule has been regarded as a tumor suppressor. In contrast, de novo expression of CEACAM1 is found with the progression of malignancy and metastatic spread in a large array of cancer tissues which include melanoma, Non Small cell Lung carcinoma (NSCLC) as well as bladder, prostate, thyroid, breast, colon and gastric carcinomas. DISCUSSION: We report and discuss the most significant findings confirming at immunohistochemical and clinical level the correlation between poor prognosis and expression of CEACAM1 on the cell surface of tumors.

In questo articolo abbiamo focalizzato il nostro interesse su di una classe di molecole di adesione e più in particolare sul CEACAM1 che in diversi studi è stato osservato essere coinvolto nella trasformazione tumorale attraverso complessi meccanismi di modulazione e di alterata regolazione. OBIETTIVO: L'espressione di CEACAM1 risulta spesso associata con l'abolizione della oncogenicità di linee cellulari trasformate e pertanto questa molecola di adesione è stata considerata alla stregua di un immunosoppressore tumorale. DISCUSSIONE: In contrasto con questa osservazione, in molti casi l'espressione de novo di CEACAM1 risulta essere associata con la progressione tumorale e la metastatizzazione di diverse forme di cancro che includono il melanoma, il carcinoma polmonare a non piccole cellule, il carcinoma della vescica, della prostata, mammario, tiroideo e del carcinoma gastrico e del colon. In questo articolo riportiamo i dati più significativi della letteratura corrente che dimostrano attraverso studi immunoistochimici e clinici una stretta correlazione fra prognosi infauste ed espressione del CEACAM1 sulla superficie di cellule tumorali.