Search

Palmoplantar keratosis is a frequent hereditary disorder of keratinization in humans that have been classified into diffuse, punctate and focal forms according to the pattern of hyperkeratosis on the pal and soles. Various clinically, histopathologically and genetically distinct phenotypes can be diagnosed. Diffuse palmoplantar keratodermas can be further subdivided by the presence of epidemlysis on histopathology into epidermolytic form and non-epidermolytic form. The late onset non-epidermolytic palmoplantar keratoderma was found associated with oesophageal cancer. The causative locus designated as TOC(Tylosis with oesophageal cancer) mapped to a small region on chromosome 17q25. Frequent allelic loss was found overlapping the region in sporadic oesophageal, ovarian and breast cancers. Positional cloning and candidate gene analysis will allow identification and characterization of the TOC gene which may also be implicated in cancer development.

Introduction and Objectives: It is reported that cytokeratin 19 (CK-19) mRNA is not expressed in the peripheral blood cells of the healthy subjects (Am. J. Pathol. 142: 1111. 1993). Detection of DNA fragments of CK-19 in the peripheral blood suggests the existence of epithelial malignant tumor cells. In this study, we detected CK-19 genes in peripheral blood of patients with urogenital malignancy, and thus clarified the possibility of understanding tumor expansion., Methods: Mononuclear cells were separated from the peripheral blood of 39 patients with urogenital tumor and 9 controls. Total cellular RNA was extracted according to the method described elsewhere. The CK-19 gene expression was investigated using nested reverse transcription polymerase chain reaction (nested RT-PCR) and confirmed by Southern Blotting. These results were compared to the clinical stages., Results: CK-19 mRNA was not detected in any of 9 controls. CK-19 mRNA was detected in 3 out of the 10 bladder cancer cases. Two had metastases and 1 had muscle invasion without metastasis. One of 6 urothelial cancer case of the upper urinary tract showed positive amplification, and had liver, bone and lymphnode metastases. After one course of chemotherapy, mRNA became negative. In prostate cancer cases, three among 7 were positive and all 3 cases had distant metastases. In renal, testicular and penile cancer cases, the positive ratio were 3/6, 1/8 and 2/2, respectively. All positive cases of renal and testicular cancer had distant metastases, but one case of penile cancer had no metastasis., Conclusion: The detection of CK-19 mRNA in the circulating blood by nested RT-PCR makes it possible to detect micrometastasis, to evaluate therapeutic effects and to predict the prognosis.

While not all circulating tumor cells survive, one could postulate that patients with circulating tumor cells might be candidates for adjuvant chemotherapy because of the risk of relapse. Recently, reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of circulating tumor cells has been suggested as a potential technique for staging of cancer. In malignant melanoma, the detection of circulating melanoma cells by tyrosinase RT-PCR correlated with the clinical stage of patients and was an independent prognostic factor for recurrence. A strong association was found between the detection of neuroblastoma cells in circulation by tyrosine hydroxylase RT-PCR with bone marrow micrometastasis. This method may be of use to identify early signs of relapse in disease-free patients. In prostatic cancer, the frequency of positivity for detection of circulating tumor cells in peripheral blood by PSA RT-PCR increased with tumor stages but a significant proportion of patients with metastatic disease were negative. The prognostic significance of the detection of tumor cell in blood in other epithelial tumors is not established and will require further long-term follow-up study.

An in situ hybridization method was applied to detect keratin mRNA expression and human origin of xenotransplanted human tracheobronchial epithelium into nude mice. Tissues from eight tracheas repopulated with cells from five different donors were used. A K6 (56 kd) human keratin cDNA (KA-1) and a K14 (50 kd) cDNA (KB-2) were radiolabeled with 3H-dATP/TTP and used as probes to study changes in keratin mRNA expression in various lesions of the tracheobronchial epithelium. To identify human tissues xenotransplanted into nude mice, high-molecular-weight DNAs extracted from human or mouse tissues were sonicated, nick-translated with 32p-dCTP, and used as probes. Dot-blot hybridization of 32p-labeled DNA probes revealed clear species-specific signals and cells of human origin were distinguishable by in situ hybridization with sonicated human DNA probe. In situ hybridization with either KA-1 or KB-2 probe showed similar localization of silver grains in all histologic types in consecutive tissue lesions of xenotransplanted tracheobronchial epithelia. Very few grains were seen over cells of simple, pseudostratified, or stratified epithelia two to three cell layer thick. Nonkeratinizing stratified hyperplastic epithelia of more than three cell layers showed uniform localization of grains throughout the lesions. In contrast, epidermoid metaplasias exhibit a dense and localized pattern of grains on the basal and parabasal cell layers with a decrease in grain density toward the surface layers. In situ hybridization with sonicated DNA probes provided a powerful tool for verifying the human origin of xenotransplanted tissues in nude mice, showing several advantages, simple preparation of probes, high sensitivity, and applicability to all types of tissues and cells. With KA-1 and KB-2 probes, the different localization pattern of keratin mRNAs in different epithelial lesions were demonstrated. It was of particular interest that an ordered program of keratin mRNA expression proportional to the level of cellular differentiation was observed in epidermoid metaplasias. Both of these probes serve as keratinization markers of human tracheobronchial epithelial lesions.