bromochloroacetic-acid and Hematologic-Neoplasms

Skin samples taken from 6 female patients receiving allogeneic bone marrow transplants (BMT) from male siblings (n=5) or from unrelated human leukocyte antigen (HLA)-matched male donor (n=1) due to hematological malignancies were studied for the presence of donor cells. One nontransplanted male and 1 female control that received female BM were used as further controls of the technique. Skin biopsies were taken from the scalp and the back from each patient 12-16 years after the successful BMT. We have found donor chimerism in all of the 6 patients in both of their biopsies. Using single and double immunostainings in combination with Y chromosome hybridization, we observed that there are cytokeratin-expressing donor-derived cells in the epidermis of all the 6 patients, the numbers being slightly higher in the scalp (0.37%-1.78%) than in the back (0.32%-1.08%) biopsies. The indication for BMT, and the age of the patient did not seem to have any effect on the numbers found. A few of the double-labeled cells also stained for Ki67, a marker of cellular proliferation, suggesting that the engrafted cells were able to further divide in the epidermis. In 2 patients we observed patches of donor keratinocytes within the epidermis, suggesting a clonal origin. We conclude that in agreement with some and in contrast to other published studies, BM-derived circulating cells are able to engraft in the human skin and to further proliferate there and thus contribute to tissue renewal. These data raise the possibility to use BM cells in regenerative medicine to help in extended injuries, large surface burns, or lack of skin due to other reasons.

Topics: Adult; Back; Biopsy; Bone Marrow Transplantation; Chimera; Chromosomes, Human, Y; Female; Hematologic Neoplasms; Humans; Keratinocytes; Keratins; Male; Middle Aged; Scalp; Skin; Tissue Donors; Transplantation, Homologous

Various molecular markers have been used for the detection of circulating breast cancer cells in blood by reverse transcriptase-polymerase chain reaction (RT-PCR). Using nested RT-PCR, we compared the specificity and sensitivity of human mammaglobin (hMAM), epidermal-growth-factor receptor (EGF-R), and cytokeratin 19 (CK-19) expression as markers for circulating carcinoma cells in the peripheral blood of patients with breast cancer. Blood samples from 12 patients with ductal carcinoma in situ, 133 patients with invasive breast cancer, 20 patients with hematological malignancies, 31 healthy volunteers, and tumor tissues from 40 patients with invasive breast cancer were screened for mRNA encoding hMAM, EGF-R, or CK-19 by nested RT-PCR. In all breast cancer tissues, mRNA for hMAM, EGF-R, and CK-19 was detectable. In blood samples from patients with invasive breast cancer, 11 (8%), 13 (10%), and 64 (48%) were positive for mRNA encoding hMAM, EGF-R, or CK-19, respectively. Blood samples from none of the healthy volunteers and patients with hematological disorders were positive for hMAM, while CK-19 mRNA was found in the blood of 12 (39%) healthy volunteers and transcripts for EGF-R and CK-19 were detectable in 5 (25%) and 2 (10%), respectively, of the patients with hematological malignancies. Only hMAM mRNA expression in blood correlated with clinical parameters such as nodal status, metastasis, and CA 15-3 serum levels. In summary, hMAM transcripts detectable in blood by RT-PCR represent the most specific molecular marker for hematogenous spread of breast cancer cells. With the nested RT-PCR method, aberrant EGF-R mRNA expression might occasionally be found in hematological malignancies, whereas CK-19 mRNA expression proved to be rather nonspecific. The prognostic value of hMAM RT-PCR-based tumor cell detection in peripheral blood should be further tested and validated in prospective studies.

Topics: Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; ErbB Receptors; Female; Gene Expression; Hematologic Neoplasms; Humans; Keratins; Mammaglobin A; Middle Aged; Neoplasm Invasiveness; Neoplasm Proteins; Tumor Cells, Cultured; Uteroglobin