Immunohistochemical expression of mitochondrial membrane complexes (MMCs) I, III, IV and V in malignant and benign periampullary epithelium: a potential target for drug therapy of periampullary cancer?
BACKGROUND
Mitochondrial membrane complexes (MMCs) are key mediators of cellular oxidative phosphorylation, and inhibiting them could lead to cell death. No published data are available on the relative abundance of MMCs in different periampullary cancers. Therefore, we studied the expression profile of MMCs I, III, IV and V in periampullary cancers, reactive pancreatitis, normal pancreas and chronic pancreatitis.


METHODS
This was a retrospective study on tissue microarrays constructed from formalin-fixed paraffin-embedded tissue from 126 consecutive patients (cancer = 104, chronic pancreatitis = 22) undergoing pancreatic resections between June 2001 and June 2006. 78 specimens of chronic pancreatitis tissue were obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from the resection specimens in a total of 30 patients. Metastatic tumours in 61 regional lymph nodes from 61 patients were also studied.


RESULTS
MMCs I, III, IV and V were highly expressed (p < 0.05) in all primary periampullary cancers compared with metastatic lymph nodes and adjacent benign pancreas. MMCs III, IV and V were highly expressed in all cancers regardless of type compared with chronic pancreatitis (p < 0.05). Higher expression of MMCs I and V was associated with better survival and may, in part, relate to lower expression of these MMCs in poorly differentiated tumours compared with well and moderately differentiated tumours.


CONCLUSIONS
Differential expression of MMCs III, IV and V in primary periampullary cancers compared with adjacent benign periampullary tissue and chronic pancreatitis is a novel finding, which may render them attractive anticancer targets.
Aloysius
Mark M
MM
Division of Gastrointestinal Surgery, Nottingham Digestive Diseases Centre, NIHR Biomedical Research Unit, Nottingham University Hospitals, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Zaitoun
Abed M
AM
Bates
Timothy E
TE
Ilyas
Mohammad
M
Constantin-Teodosiu
Dumitru
D
Rowlands
Brian J
BJ
Lobo
Dileep N
DN
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation; D004848:Epithelium / Q000187:drug effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D009362:Neoplasm Metastasis; D018384:Oxidative Stress; D010179:Pancreas / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000628:therapy; D010195:Pancreatitis / Q000473:pathology; D010766:Phosphorylation; D012189:Retrospective Studies
D000970:Antineoplastic Agents