Intestinal, intestinal-type and intestine-localized metastatic adenocarcinoma. Immunohistochemical approach to the differential diagnosis.

The pathologist is often called to define the origin of tumors through the help of ancillary studies, mainly immunohistochemical stainings. In this setting, the differential diagnosis between intestinal adenocarcinomas, other tumors with intestinal-type morphology, and adenocarcinomas metastatic to the bowel can be particularly difficult. In such cases, an accurate assessment of the disease is required to address the patients to the optimal treatment. Immunohistochemistry offers the use of multiple antibodies: the integrated evaluation of specific stainings can lead to a correct diagnosis. Particularly, the use of cytokeratins, mucins, and ß-catenin could be of great help in most cases. In addition, recently, novel specific markers such as SATB2 and AMACR have been introduced, improving the utility of immunohistochemistry in the differential diagnosis of intestinal-type and intestinal adenocarcinomas.

Deregulation of HOX B13 expression in urinary bladder cancer progression.

Urinary bladder cancer is a common malignancy in industrialized countries. More than 90% of bladder cancer originates in the transitional cells. Bladder transitional cancer prognosis is, according to the most recent definition related to the level of tumor infiltration, characterized by two main phenotypes, Non Muscle Invasive Bladder Transitional Cancer (NMIBC) and Muscle Invasive Bladder Transitional Cancer (MIBC). The genetic profile and the clinical course of the two subtypes are completely different, however among NMIBC the prognosis is not completely predictable, since 20% of the cases experience a relapse, even in the form of MIBC. It has recently been reported that the chromosomal region 12q13-15, containing crucial cancer genes such as MDM2, CDK4, GLI and an entire cluster of HOX genes, is amplified in bladder cancer. HOX genes codify for transcriptionl factor, involved in embryonal development and cancer progression, with main nuclear expression. Particularly it was also described the strong involvement of HOX B13 in several tumors of urogenital system. In this study we have been investigated, by immunohistochemisty and quantitative Real Time PCR, the HOX B13 expression in bladder cancer evolution and progression, evaluating its ability to discriminate between NMIBC and MBCI phenotypes. Cytoplasmic HOX B13 delocalization significantly relates with muscle invasion (p 0.004). In addition in the series of NMIBC nuclear HOX B13 expression loss is significantly associated to shorter disease free survival (p-value=0.038) defining a potential prognostic role. Overexpression of HOX B13 in more aggressive phenotype is also demonstrate at gene level by quantitative RT-PCR. The de-regulation and delocalization of HOX B13 in urinary bladder cancer supports again the important role of HOX genes in tumor evolution and represents a starting point to establish an integrated analysis, in which HOX genes represent important prognostic and predictive markers for bladder cancer.