Medical audit of diagnostic mammography examinations: comparison with screening outcomes obtained concurrently.

OBJECTIVE: We performed a medical audit of our diagnostic mammography practice and compared clinical outcomes with those of screening mammography examinations performed concurrently. MATERIALS AND METHODS: We analyzed 46,857 consecutive mammography examinations (10,007 diagnostic, 36,850 screening) from 1997 to 2000, including data on demographics, image interpretation, and biopsy (including size, nodal status, and cancer stage). RESULTS: The mean age at diagnostic mammography was 55.8 years (mean age at screening mammogram, 59.1 years; p < 0.0001). Among patients who underwent diagnostic examinations, 14.7% had a strong or very strong family history of breast cancer (screening, 11.6%; p < 0.0001). Examination findings were interpreted as abnormal in 14.4% (screening, 5.2%; p < 0.0001). Biopsy was performed in 11.9% (screening, 1.4%; p < 0.0001). Forty-six percent of the biopsies were positive for malignancy (screening, 38%; p < 0.0001). The cancer detection rate was 55 per 1000 (screening, 5/1000; p < 0.0001). Of cancers found, 74.4% were stage 0 or I (screening, 89.3%; p < 0.0001), average size was 18.0 mm (screening, 12.9 mm; p < 0.0001), and axillary nodes were positive for malignancy in 19.9% of invasive cancers (screening, 6.3; p < 0.0001). Differences between diagnostic and screening outcomes were attributable predominantly to the subgroup of diagnostic examinations performed for evaluation of palpable masses. CONCLUSION: Medical auditing of diagnostic mammography examinations yields substantially different results compared with those of screening examinations, including different patient demographics; higher number of positive biopsies; higher cancer detection rates; and larger, more advanced-stage cancers. Diagnostic and screening data should be segregated during auditing, or if this is not possible, analysis of combined results should be based on known differences between diagnostic and screening outcomes.

Parathyroid hormone-related protein. Evidence for secretion of a novel mid-region fragment by three different cell types.

The cDNA-predicted amino acid sequence of parathyroid hormone-related protein (PTHrP) contains multiple basic amino acid motifs, suggesting that PTHrP undergoes extensive post-translational processing prior to secretion. The secretory forms of the peptide are currently unknown. To identify these secretory forms, medium was harvested from three cell types: human renal carcinoma (SKRC-1) cells, human keratinocytes, and rat insulinoma cells stably transfected with the cDNA for PTHrP(1-141) (RIN-141 cells). Amino-terminal species were immunopurified using an anti-PTHrP(1-36) column, and mid-region species using an anti-PTHrP(37-74) column. PTHrP peptides in medium and in cell extracts were further resolved by reverse phase high performance liquid chromatography (RP-HPLC) and identified using region-specific immunoassays. SKRC-1 and RIN-141 cells secreted three distinct amino-terminal species and a novel, non-amino-terminal, mid-region fragment. Sequence and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis indicated that the RIN-141 cell mid-region fragment begins at amino acid 38 of the cDNA-predicted sequence and is approximately 70 amino acids in length. Comparison of RP-HPLC elution patterns suggests that SKRC-1 cells and keratinocytes secrete a similar or identical mid-region fragment. Immunofluorescence studies revealed a Golgi pattern for the amino-terminal species and a secretory granule pattern for the mid-region fragment. These studies indicate that 1) multiple PTHrP species are secreted, including a novel mid-region fragment; 2) Arg37 serves as a cleavage site in at least three cell types; 3) PTHrP(1-36) is likely to be an authentic secretory form of PTHrP; and 4) the mid-region fragment appears to be packaged into secretory granules. The marked interspecies conservation of this mid-region PTHrP suggests that it will have important biological functions.