Intracystic Papillary Carcinoma: A Closer Look into Its Relationship with In Situ and Invasive Carcinoma: Array Comparative Genomic Hybridization Study of 14 Cases
Thaer Khoury, Qiang Hu, Song Liu, Jianmin Wang. Roswell Park Cancer Institute, Buffalo, NY
Background: Classifying ICPC under invasive (IDC) or in situ carcinoma (DCIS) is still a matter of debate. The purpose of this study is to explore the genomic relationship of this tumor to its concurrent IDC or DCIS using array comparative genomic hybridization (aCGH).
Design: ICPC cases (n=14) were classified into 3 categories, pure ICPC (n=7), with concurrent DCIS (n=5) and with concurrent IDC (n=2). Each component was dissected using laser capture microdissection. DNA was extracted and aCGH was performed. The test of difference in copy number changes among ICPC, DCIS and IDC was carried out using CGHMultiArray.
Results: ICPC had common copy number change including 16p gain, 16q loss, and 1q gain. In addition, 7q loss, 8p23.3-8p21.1 loss, 11q14.1 to 11q22.1 loss, 11q22.1 to 11q25 loss, 9p13.1-9q12 loss, and 1q21.3-1q23.1 gain were found in variable number of cases. Hierarchical agglomerative clustering of samples using probe log2 ratio revealed that the three components could not be separated into different cluster. Moreover, 4 of 5 DCIS cases and both IDC cases clustered with the concurrent ICPC. The median and range for the proportions of changed genome was 8% (3.7% to 19.1%) for ICPC, 6.2% (5.9% to 11.9%) for DCIS, and 2.2 (0.09% to 10.9%) for IDC (p=0.06, Wilcox rank sum test). The mean probability of copy number changes for DCIS is similar to ICPC with the following additional focal changes: 8q22.2 to 8q22.3 gain, 8q24.3 gain, and 11q25 loss in 3 of 6 cases, and 12q24.31-12q24.33 loss in 2 of 6 cases. A group of genes involved in cell adhesion and motility was found in DCIS, listed in table 1.
Conclusions: 1. ICPC shares all major copy number variation with concurrent DCIS and IDC, which suggest that all tumors arise from one stem cell. 2. The overall molecular change in ICPC is closer to DCIS than to IDC, which may explain its indolent clinical behavior. 3. DCIS acquires motility/adhesion molecular changes. So, we suggest that these changes permits the neoplastic cells to migrate from ICPC and colonize the surrounding ducts, but does not give it the required genetic changes for stromal invasion.
|SPAG1||Gain||8q22.2||Pro- cell motility|
|RHPN1||Gain||8q24.3||Coordinated assembly of focal adhesions|
|SCRIB||Gain||8q24.3||Pro-cell migration and cell polarity|
|MIR661||Loss||11q.25||Anti- cell motility|
|NTM||Loss||11q.25||GPI-anchored cell adhesion molecule|
|OPCML||Loss||11q.25||Cell adhesion molecule|
|JAM3||Loss||11q.25||Junctional adhesion molecule|