Epigenetic Contribution of High-Mobility Group A Proteins to Stem Cell Properties.

High-mobility group A (HMGA) proteins have been examined to understand their participation as structural epigenetic chromatin factors that confer stem-like properties to embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and cancer stem cells (CSCs). The function of HMGA was evaluated in conjunction with that of other epigenetic factors such as histones and microRNAs (miRs), taking into consideration the posttranscriptional modifications (PTMs) of histones (acetylation and methylation) and DNA methylation. HMGA proteins were coordinated or associated with histone and DNA modification and the expression of the factors related to pluripotency. CSCs showed remarkable differences compared with ESCs and iPSCs.

Cutaneous Osteoblastic Osteosarcoma: Report of 2 New Cases Integrated With SATB2 Immunohistochemistry and Review of the Literature.

We report 2 cases of primary dermal osteosarcoma. The patients were an 88-year-old man and a 72-year-old man complaining of masses occurring in the ear pavilion and the palm, deemed suspicious for basal cell carcinoma and metastatic colonic carcinoma, and were treated by resection. Microscopically, both featured a dermal lesion mostly composed of atypical spindle cells within a fibrous to hyaline matrix often showing mineralization. Osteoid material was rimmed by atypical tumor cells and was also associated with osteoclast-like giant cells. Tumor cells were positive for SATB2 and negative for markers of epithelial (low-molecular and high-molecular weight cytokeratins, epithelial membrane antigen, p63), melanocytic (S100 protein, HMB45, Melan A), and skeletal/smooth muscle differentiation (desmin, myogenin). No further therapy has been administered. Follow-up at 6 (case 1) and 8 months (case 2) was uneventful. A brief differential diagnosis discussing cutaneous tumors capable of showing osseous differentiation is summarized, along with a review of the pertinent literature. The specificity and sensitivity of SATB2 is also shortly addressed.

Liver involvement by multiple myeloma presenting as hypervascular focal lesions in a patient with chronic hepatitis B infection.

Extramedullary myeloma refers to the infiltration of neoplastic monoclonal plasma cells in either organs or soft tissues. The disease is clinically and radiologically underestimated compared with the autopsy findings and is usually associated with a more aggressive clinical course and poorer outcome. A minority of patients with extramedullary myeloma show hepatic involvement, usually in the form of diffuse parenchymal infiltration. When focal infiltration is present, variable imaging findings have been described both on CT scan and MRI. We report the case of a 63-year-old male with hepatitis B virus-related liver disease and biopsy-proven multiple myeloma involving the liver, manifesting as hypervascular focal liver lesions on MRI. A brief review of the literature is also proposed.

Mucinous tubular and spindle cell carcinoma of the kidney: a rare case diagnosed in the early postpartum.

A 27-year-old women requesting assistance for an unspecified abdominal pain localized in the right flank that worsened after a recent delivery was discovered to have a solid mass in the upper pole of her right kidney. Radiological findings showed benign characteristics but without a clear diagnosis. Subsequently, a laparotomic nephron-sparing enucleation of a solid, encapsulated, brownish-white mass, localized in the cortical portion of the upper kidney pole, was performed. Pathological examination of the specimen showed a rare mucinous tubular and spindle cell carcinoma with an almost total mucinous component. To our knowledge, this is the first case of this disease discovered during pregnancy or puerperium. A multidisciplinary approach should be mandatory in order to correctly recognize and treat such a rare disease and to avoid administration of excessive adjuvant treatment to patients with a low-grade malignancy during pregnancy or puerperium.

The expression of the high-mobility group A2 protein in colorectal cancer and surrounding fibroblasts is linked to tumor invasiveness.

Tumor staging of colorectal cancer is typically based on conventional TNM and Dukes classifications. However, additional information could be useful, and there is a significant interest in identifying molecular markers that are related to genetic or epigenetic processes. Using immunohistochemistry, we analyzed the expression of the high-mobility group A2 (previously high-mobility group 1-C [HMGI-C]) protein in 103 colorectal cancer cases to determine its use as a biomarker in colorectal cancer to integrate morphological staging. We found a progressive increase of the high-mobility group A2 protein expression in colorectal cancer tumor samples from cases in which all of the tumor cells were negative up to cases in which all of the tumor cells stained positive. Increased high-mobility group A2 expression is strongly associated with an increase in tumor invasiveness, which was measured through both budding and vascular invasion (P < .0001). Kaplan-Meier estimates showed a decrease in overall survival when vascular invasion is present (P = .023). Moreover, a fraction of the analyzed samples showed high-mobility group A2-positive stromal fibroblasts. Although high-mobility group A2-positive tumors were associated with cell invasiveness, high-mobility group A2-positive stromal fibroblasts were correlated with less invasive tumors. High-mobility group A2 protein expression could be used as a prognostic marker to provide prospective information on patient outcome, complementing the data obtained using conventional pathologic staging systems.

Ovarian psammocarcinoma with peritoneal implants.

A case of ovarian psammocarcinomas with omental and peritoneal implants in a 48-year-old woman was treated with total hysterectomy, bilateral oophorectomy and omentectomy. Two years later there was no sign of recurrent disease.

Balance between cell division and cell death as predictor of survival in patients with non-small-cell lung cancer.

OBJECTIVE: To evaluate the prognostic value of the balance between apoptosis and proliferation in non-small-cell lung cancer (NSCLC). METHODS: Paraffin-embedded sections from a consecutive series of radically resected NSCLCs were scored for apoptosis (in situ DNA nick end labeling assay) and proliferation (immunohistochemistry for MIB-1). A total of 1,000 cells were counted per case, to obtain apoptotic (AI) and MIB-1 indices. Other potential prognostic indicators (pT, pN, pStage and histology) and p53 status were also evaluated. RESULTS: Univariate analysis showed that adenocarcinomatous histotype (p = 0.03), nodal involvement (p = 0.04), higher pStage (p = 0.001) and the combination of low AI and high MIB-1 expression (p = 0.03) were associated with poorer outcome. The significant prognostic value of the combination 'low AI/high MIB-1' was also confirmed in a multivariate analysis after adjustment for other covariates. CONCLUSION: These results underline the importance of considering apoptosis and proliferation together to identify a subgroup of NSCLC associated with poor survival.

Expression and localization of the homeodomain-containing protein HEX in human thyroid tumors.

Homeobox genes are involved in neoplastic transformation of both epithelial and hemopoietic tissues. The divergent homeobox gene HEX is expressed in the anterior visceral endoderm during early mouse development and in some adult tissues of endodermal origin, including liver and thyroid. Whereas a role in leukemyogenesis has been proposed already, few data are available on the involvement of HEX in human epithelial tumors. Herein, we analyzed HEX expression and subcellular localization in a series of 55 human thyroid tumors and in several tumoral cell lines. HEX mRNA was detected by RT-PCR either in normal tissues or in thyroid adenomas and differentiated (papillary and follicular) carcinomas. HEX mRNA was also expressed in most undifferentiated carcinomas. Subcellular localization of HEX protein was investigated by immunohistochemistry. In normal tissues and adenomas, HEX protein was present both in nucleus and cytoplasm. In contrast, both differentiated and undifferentiated carcinomas, as well as the tumoral cell lines investigated, showed HEX protein only in the cytoplasm. These findings suggest that regulation of HEX entry in the nucleus of thyrocytes may represent a critical step during human thyroid tumorigenesis.