Breast density, scintimammographic (99m)Tc(V)DMSA uptake, and calcitonin gene related peptide (CGRP) expression in mixed invasive ductal associated with extensive in situ ductal carcinoma (IDC + DCIS) and pure invasive ductal carcinoma (IDC): correlation with estrogen receptor (ER) status, proliferation index Ki-67, and histological grade

Abstract

Background: We evaluated the variation of calcitonin gene related peptide (CGRP) expression in patients with mixed invasive with extensive in situ ductal carcinomas (IDC + DCIS) and pure IDC, in relation to mammographic breast density (%BD), proliferation-seeking radiotracer (99m)Tc(V) dimercaptosuccinic acid (DMSA) uptake (scintimammographic-SMM), proliferation index Ki-67, and estrogen receptor (ER) status. We also assessed CGRP expression with histological grade.

Methods: We studied retrospectively 24 women with suspicious findings on mammography who were evaluated preoperatively with (99m)Tc(V)DMSA scintimammography. Histology revealed 12 IDC (grade II in 8, grade III in 4 patients; mean size ± SD, 2.6 ± 1.3 cm; mean age ± SD, 66.5 ± 13.1 years) and 12 IDC + DCIS (grade II in 6, grade III in 6 patients; DCIS component mean size ± SD, 5.3 ± 1.8 cm; IDC component mean size ± SD, 2.5 ± 1.1 cm; mean age ± SD, 58.5 ± 15.1 years). Immunohistochemistry for CGRP, Ki-67, and ER status was performed in all 24 surgical specimens. BD and SMM were calculated by computer-assisted methods and were statistically correlated with CGRP expression. BD, SMM, Ki-67, and ER were statistically compared between IDC and IDC + DCIS, whereas CGRP, Ki-67, and ER were compared between patients with BD >25 and <25%. CGRP was also compared (t test) between grade II and grade III in both groups.

Results: Overall positive correlation was found between BD and CGRP (r = 0.577, P < 0.001). Positive correlation was established between SMM and CGRP only in IDC + DCIS (r (SMM(IDC+DCIS)-CGRP) = 0.634, P < 0.05). CGRP and Ki-67 were significantly higher in patients with BD >25% compared with <25% BD patients (P = 0.00008 and P = 0.014, respectively). BD and SMM were significantly higher in CGRP(+) than in CGRP(-) patients as well as in IDC + DCIS compared with IDC. Ki-67 was significantly higher, whereas ER was significantly lower, in IDC + DCIS than in IDC. In all patients, CGRP was significantly higher in grade II as compared with grade III (P = 0.005). In the mixed group (IDC + DCIS), grade II cancers had also significantly higher CGRP values as compared with grade III ones (P = 0.004). In pure IDC, no statistical difference was found between grade II and III (P = 0.4).

Conclusions: ΒD, SMM, CGRP, and Ki-67 were significantly increased, whereas ER was significantly decreased, in IDC + DCIS as compared with IDC, indicating that IDC + DCIS is an entity that is more aggressive, ER independent, and possibly associated with a pathway linked to stromal involvement and CGRP activity.