Breast density, scintimammographic 99mTc(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

We evaluated the variation of calcitonin gene related peptide (CGRP) expression in patients with mixed invasive with extensive insitu 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. We studied retrospectively 24 women with suspicious findings on mammography who were evaluated preoperatively with (99m)Tc(V)DMSA scintimammography. Histology revealed 12 IDC (gradeII in 8, gradeIII in 4 patients; mean size±SD, 2.6±1.3cm; mean age±SD, 66.5±13.1years) and 12 IDC+DCIS (gradeII in 6, gradeIII in 6 patients; DCIS component mean size±SD, 5.3±1.8cm; IDC component mean size±SD, 2.5±1.1cm; mean age±SD, 58.5±15.1years). 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 gradeII and gradeIII in both groups. 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 gradeII as compared with gradeIII (P=0.005). In the mixed group (IDC+DCIS), gradeII cancers had also significantly higher CGRP values as compared with gradeIII ones (P=0.004). In pure IDC, no statistical difference was found between gradeII and III (P=0.4). 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.