Fluorescence and reflectance spectroscopy could be a valuable tool for examining the superficial margin status of excised breast tumor specimens, particularly in the form of spectral imaging to examine entire margins in a single acquisition.

Introduction Mammary columnar cell lesions with atypia have been receiving increased scrutiny in view of their association with atypical hyperplasia (AH) and carcinoma. However, the few retrospective outcome studies performed have failed to establish an increased risk for recurrence or carcinoma on long-term follow-up. Materials and Methods We evaluated the overall cancer risk for 1261 biopsies with columnar cell lesions (CCL), in 4569 women from the Nashville Breast Cohort who were biopsied between 1969 and 1988. Based on Schnitt and Vincent-Salomon’s classification, we also classified 229 biopsies with CCL into three categories: without hyperplasia or atypia, with hyperplasia lacking atypia, and with atypia. Using a nested case-control design, we compared the risks of invasive cancer associated with these three categories. Results We observed a 2-to-3-fold increase in the occurrence of AH in the presence of CCL versus in their absence (P < 0.005). Relative risk of invasive breast cancer for women with both AH and CCL compared to those with AH alone did not differ significantly (RR=1.55, P = 0.29). The presence of CCL alone was associated with a mild increase in the overall cancer risk (RR=1.47; P = 0.05). In the nested case-control study, no significant risk difference was observed among the three categories of CCL. Conclusion We observed a positive association between CCL and AH. The evidence that CCL by itself significantly elevates breast cancer risk is not well supported. However, a finding of CCL on benign breast biopsy may indicate the presence of AH, a more worrisome lesion.

For a given diagnostic problem, important considerations are the relative performances of the various optical biopsy techniques. A comparative evaluation of fluorescence, diffuse reflectance, combined fluorescence and diffuse reflectance, and Raman spectroscopy in discriminating different histopathologic categories of human breast tissues is reported. Optical spectra were acquired ex vivo from a total of 74 breast tissue samples belonging to 4 distinct histopathologic categories: invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS), fibroadenoma (FA), and normal breast tissue. A probability-based multivariate statistical algorithm capable of direct multiclass classification was developed to analyze the diagnostic content of the spectra measured from the same set of breast tissue sites with these different techniques. The algorithm uses the theory of nonlinear maximum representation and discrimination feature for feature extraction, and the theory of sparse multinomial logistic regression for classification. The results reveal that the performance of Raman spectroscopy is superior to that of all others in classifying the breast tissues into respective histopathologic categories. The best classification accuracy was observed to be approximately 99%, 94%, 98%, and 100% for IDC, DCIS, FA, and normal breast tissues, respectively, on the basis of leave-one-sample-out cross-validation, with an overall accuracy of approximately 99%.

Reduced levels of human myeloid nuclear differentiation antigen (MNDA) gene transcripts have been detected in both familial and sporadic cases of myelodysplastic syndromes (MDS). Numerous reports implicate elevated apoptosis/ programmed cell death and death ligands and their receptors in the pathogenesis of MDS. MNDA and related proteins contain the pyrin domain that functions in signaling associated with programmed cell death and inflammation. We tested the hypothesis that MNDA is involved in the regulation of programmed cell death in human myeloid hematopoietic cells. Clones of K562 cells (MNDA-null) that expressed ectopic MNDA protein were established using retroviral transduction. MNDA-expressing K562 clones were resistant to tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis, but were not protected from programmed cell death induced with genotoxic agents or H 2 O 2 . MNDA protein expression assessed in control and intermediate and high-grade MDS marrows showed several patterns of aberrant reduced MNDA. These variable patterns of dysregulated MNDA expression may relate to the variable pathophysiology of MDS. We propose that MNDA has a role regulating programmed cell death in myeloid progenitor cells, and that its down-regulation in MDS is related to granulocytemacrophage progenitor cell sensitivity to TRAIL-induced programmed cell death.

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