Claudins as diagnostic and prognostic markers in gynecological cancer.

Claudins are the main protein components of tight junctions (TJs) which function as selective barriers by controlling paracellular diffusion, maintain cellular polarity and play a role in signal transduction. The expression pattern of the 24 known members of the claudin family proved to be organ and tissue specific. The up- or downregulation of individual claudins has been described, especially during carcinogenesis. A significant increase of claudins-1 and -7 was detected in premalignant cervical lesions and invasive cancer compared with normal cervical epithelia. Claudins-3 and -4 were elevated in endometrial cancer. Claudin-1 overexpression characterized type II (seropapillary) endometrial carcinoma, while claudin-2 was elevated in type I (endometrioid) carcinoma. Claudins-3 and -4 were highly expressed in serous ovarian carcinoma. The expression data on claudins in different premalignant and malignant alterations suggest that these proteins might serve as diagnostic and prognostic markers and might be targets for future therapy.

Hepatitis viruses and hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is among the most frequent malignancies worldwide. Hepatitis viruses, such as the hepatitis B virus (HBV) and hepatitis C virus (HCV) are undoubtedly listed in the etiology of HCC. Studies show that, in the near future, viral hepatitis will carry increasing weight in the etiology of HCC. This review briefly discusses the known carcinogenic effects of HBV and HCV in the light of experimental and human studies. The data show that viral proteins may directly interfere with gene products responsible for cell proliferation and cell growth. Many other signal transduction cascades may be affected as well. Direct integration of HBV viral sequences into the host genome increases the genomic instability. The genomic imbalance allows the development and survival of malignant clones bearing defected genomic information. HBV and HCV infection induces indirect and direct mechanisms through cellular damage, increased regeneration and cell proliferation, therefore enhancing the development of HCC.

Erdheim-Chester disease. Case report with autopsy findings.

Erdheim-Chester disease is a rare pathologic entity characterized by symmetrical radiodensities in the metaphyseal and the diaphyseal portions of the long bones. Fibrosis, osteoblastic cortical bone deposition, and fibroxanthomatous granulomas with lipid-laden macrophages and multinucleated giant cells, which have a particular tropism for connective and adipose tissues, are the pathologic hallmarks. To our knowledge, 27 cases have been reported in the literature since the entity was first described in 1930. Protean clinical features range from a focal and asymptomatic process to a multisystemic infiltrative disease. We describe the clinical course of a new case and review the extensive pathologic findings at autopsy, including those demonstrated by light and electron microscopy and cytochemical and immunocytochemical studies.

Third-World Hodgkin's disease at Los Angeles County-University of Southern California Medical Center.

The reported experience with Hodgkin's disease (HD) in the United States has come primarily from large referral centers that attract a predominantly white population of high socioeconomic status (SES). The majority of these patients had the nodular sclerosis (NS) histologic subtype and asymptomatic stage I/II disease. We have reviewed the records of 178 patients with HD seen within the past 17 years at Los Angeles County-University of Southern California Medical Center (LAC/USC), which is a nonreferral, government-operated facility. Our patient population was found to be heterogeneous, with 38% white, 22% black, and 36% Hispanic. Systemic "B" symptoms were noted in 62% of patients at diagnosis, and 63% had advanced disease (stage III or IV). NS pathologic subtype was present in only 52% of the group. Comparison between the races revealed: (1) Hispanics had a higher incidence of lymphocyte depleted subtype and less NS than whites (P less than .06); (2) whites had equal distribution between stages I/II and III/IV; (3) blacks and Hispanics presented more frequently with stage III/IV (P = .10); and (4) extranodal involvement occurred most often in bone in whites, and was equally distributed between liver, lung, and bone in blacks and Hispanics. We conclude that the lower SES, mixed racial population seen at our institution more closely resembles the reports of HD in Third-World countries and is characterized by advanced symptomatic disease. Further, the clinical pathologic characteristics of HD in the United States may vary significantly, depending upon the precise ethnic and socioeconomic status of the patients being served.

Extensive metastases in Peutz-Jeghers syndrome.

A 27-year-old woman with Peutz-Jeghers syndrome since age 11 years was hospitalized with a sudden onset of weakness of the right extremity, an expressive aphasia, and a three-month history of back pain. Liver and whole-body scintigrams demonstrated multiple metastatic disease; the brain scintigraphic study was compatible with infarction of the left hemisphere. Postmoretem examination two weeks after these studies showed extensive metastases in bone, liver, brain, lung, and left ovary. The source of the metastases was a malignant change from Peutz-Jeghers polyps.