Department of Nuclear Medicine, "Alexandra" University Hospital, Vas. Sofias Ave 80, Athens, 11528, Greece.
Breast Cancer. 2011 Oct;18(4):286-91. doi: 10.1007/s12282-009-0192-y. Epub 2010 Feb 9.
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.
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.
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).
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.
我们评估了降钙素基因相关肽 (CGRP) 在混合广泛原位导管癌 (IDC+DCIS) 和纯 IDC 患者中的表达变化，与乳腺密度 (%BD)、增殖性放射性示踪剂 (99m)Tc(V) 二巯丁二酸摄取 (SMM)、增殖指数 Ki-67 和雌激素受体 (ER) 状态有关。我们还根据组织学分级评估了 CGRP 表达。
我们回顾性研究了 24 名在乳腺 X 线摄影检查中出现可疑发现的女性，这些女性在术前用 (99m)Tc(V)DMSA 闪烁 SMM 进行了评估。组织学显示 12 例 IDC（8 例为 2 级，4 例为 3 级；平均大小 ± SD，2.6 ± 1.3cm；平均年龄 ± SD，66.5 ± 13.1 岁）和 12 例 IDC+DCIS（6 例为 2 级，6 例为 3 级；DCIS 成分平均大小 ± SD，5.3 ± 1.8cm；IDC 成分平均大小 ± SD，2.5 ± 1.1cm；平均年龄 ± SD，58.5 ± 15.1 岁）。所有 24 例手术标本均进行了 CGRP、Ki-67 和 ER 状态的免疫组织化学检查。BD 和 SMM 通过计算机辅助方法计算，并与 CGRP 表达进行统计学相关。对 IDC 和 IDC+DCIS 之间的 BD、SMM、Ki-67 和 ER 进行了统计学比较，而对 BD>25%和 <25%的患者之间的 CGRP、Ki-67 和 ER 进行了比较。还比较了（t 检验）两组中 2 级和 3 级之间的 CGRP。
BD 与 CGRP 之间存在总体正相关（r=0.577，P<0.001）。仅在 IDC+DCIS 中发现 SMM 与 CGRP 之间存在正相关（r(SMM(IDC+DCIS)-CGRP)=0.634，P<0.05）。BD>25%的患者与 BD<25%的患者相比，CGRP 和 Ki-67 明显更高（P=0.00008 和 P=0.014）。与 CGRP(-)患者和 IDC 相比，CGRP(+)患者的 BD 和 SMM 明显更高。Ki-67 明显更高，而 ER 明显更低，IDC+DCIS 明显高于 IDC。在所有患者中，2 级 CGRP 明显高于 3 级（P=0.005）。在混合组（IDC+DCIS）中，2 级癌症的 CGRP 值也明显高于 3 级（P=0.004）。在纯 IDC 中，2 级和 3 级之间未发现统计学差异（P=0.4）。
与 IDC 相比，IDC+DCIS 中的 BD、SMM、CGRP 和 Ki-67 明显升高，而 ER 明显降低，这表明 IDC+DCIS 是一种更具侵袭性、ER 独立且可能与与基质参与和 CGRP 活性相关的途径相关的实体。
