Metastasis of Carcinoma to Body Fluids, but Not to Regional Lymph Nodes, Is Associated with Loss of Spectrin Isoforms
Yanhua Wang, Samer N Khader, Yungtai Lo, Joseph Albanese, Howard Ratech. Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY; Albert Einstein College of Medicine, Bronx, NY
Background: Spectrin isoforms are multifunctional molecules composed of α-and β-subunits that tetramize, link ankyrin to the plasma membrane, and help integrate structure and function in complex tissues. Because βI-spectrin has been associated with worse prognosis in pancreatic carcinoma, we hypothesized that spectrin isoforms might be involved in the metastatic progression of malignant epithelial tumors. Therefore, we studied the expression of spectrin isoforms in a large number of primary carcinomas, regional lymph node metastases, and positive body fluid cytology samples.
Design: We retrospectively studied the expression of αII, βI, βII and βIII spectrin isoforms by immunohistochemically staining paraffin-embedded formalin-fixed-tissue sections of various carcinomas: primary adenocarcinoma of colon with lymph node metastasis (N = 25) and without lymph node metastasis (N = 38); comparison of paired samples from the same patient of primary tumor (N = 23) and positive body fluid cytology cell block (N = 45) originating from colon, stomach, liver, breast, uterine endometrium, ovary, and lung. We analyzed the data using McNemar's test for comparing proportions in two dependent (paired) samples.
Results: The spectrin isoforms in primary adenocarcinomas of colon were essentially unaltered whether or not there were regional lymph node metastases. In contrast, comparison of primary carcinomas to paired positive body fluid cytology samples from the same patient showed markedly reduced expression of αII and βIII spectrin isoforms in the cytology samples: 100% vs.52.2 % (P<0.0009; McNemar's test) and 91.3% vs. 26.1% (P<0.0001; McNemar's test). Many of the cytology samples lacking αII and βIII spectrins showed single carcinoma cells or small clusters of only a few carcinoma cells. Also, cytology samples that contained carcinoma cells staining positively for αII and βIII spectrins appeared weaker than corresponding primary tumors.
Conclusions: We report selective loss of αII and βIII spectrin isoforms in body fluid cytology samples positive for metastatic carcinoma, but not in primary tumors or regional lymph node metastases. We hypothesize that spectrin isoforms may have an important role in maintaining multicellular cohesion among carcinoma cells in primary tumors and regional metastases, which is lost in single or paucicellular clusters of metastatic carcinoma cells in body fluids.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 264, Wednesday Morning