Histological, immunological, and molecular methods have been used for detecting micrometastases from nonhematopoietic malignancies. Early studies utilizing cytological methods to identify circulating tumor cells demonstrated the uncertain significance of micrometastasis detection for predicting eventual recurrent disease. 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. Studies using RT-PCR thus far indicate that test results may be negative in some patients with known metastatic disease, thereby raising doubts about the utility of the method for staging of disease. In this review, we survey the relevant literature and discuss the range of current applications of histological, immunological, and molecular methods for detecting micrometastases from solid tumors in blood, bone marrow, and lymph nodes and the progress toward determining the significance of micrometastasis detection.

The clinical utility of glycated hemoglobin measurements in renal failure is controversial, given numerous earlier studies showing no correlation between glycated hemoglobin and other indicators of blood glucose control in uremic subjects. This problem is attributable, in part, to analytical interferences from carbamylated hemoglobins. We report use of a specific affinity method to measure glycated hemoglobins in a group of uremic patients, diabetic and nondiabetic, undergoing treatment by continuous ambulatory peritoneal dialysis. Concentrations of glycated hemoglobins correlated significantly with values for fasting plasma glucose (r = 0.52, n = 17, p less than 0.05) in these patients and with mean glucose measurements in five diabetic patients who used home glucose monitoring (r = 0.91, p less than 0.05). Contrary to studies with ion-exchange chromatography, our measurements of glycated hemoglobin showed no positive correlation with concentrations of urea in serum. In a separate group of patients, we found that hemodialysis sessions produced no acute effect on glycated hemoglobin. Measurements of glycated hemoglobins by analytically specific methods may thus better reflect long-term control of blood glucose in renal dialysis.

The cellular localization and hormonal controls of calbindin-D9k expression in the rodent reproductive tract have suggested new functions for this protein. The present studies were undertaken to extend the earlier studies of calbindin-D9k to the related protein, calbindin-D28k. Immunohistochemical studies revealed that calbindin-D28k was absent from female rat reproductive tissues, but was abundantly expressed in immature mouse uterus and oviduct. Immunoreactivity was restricted to the endometrial and glandular epithelium of the uterus and the oviductal epithelium. Neither 1,25-dihydroxyvitamin D- nor strontium-containing diets (to blunt 1,25-dihydroxyvitamin D production) affected expression of calbindin-D28k. Uterine, but not oviductal, calbindin-D28k decreased markedly at sexual maturity; this pattern persisted in pregnant mice and was reproduced in immature mice by the administration of estradiol (3 micrograms/day for 3 days). RNA extraction and Northern analyses demonstrated that estrogen markedly decreased calbindin-D28k mRNA abundance in the uterus, but not in the oviduct. These findings suggest that estrogen affects mammalian calbindin-D28k expression and represent a rare example of estrogen-induced down-regulation of gene expression.

We recently described (Arch Ophthalmol 1988; 106:725-6) the presence of unique calcific lesions in the eyelids of a young woman with a history of hyperphosphatemic tumoral calcinosis. Here we document that no immediate family members showed similar lesions and that none was hyperphosphatemic. Dental roentgenography revealed characteristic abnormalities in the patient that confirmed the clinical diagnosis of tumoral calcinosis. Seasonal biochemical studies demonstrated persistently increased concentrations of phosphorus and 1,25-dihydroxyvitamin D in her serum. A calcific eyelid excrescence removed from the patient, studied by x-ray diffraction, was found to consist of crystals of hydroxyapatite. Microprobe analysis indicated the major elements in the deposit to be Ca, P, S, and Cl, just as in the periarticular deposits found in tumoral calcinosis. The Ca concentration in the patient's tear fluid, measured by atomic absorption spectrometry, was within the range found in tears of healthy volunteers. Phosphorus was undetectable (less than 30 mumol/L) in tears of the patient and the volunteers. These findings suggest that the eyelid lesions represent a new manifestation of the pathological process that produces the characteristic periarticular calcific masses of tumoral calcinosis.

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