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Humoral immune response to p53 correlates with clinical course in colorectal cancer patients during adjuvant chemotherapy
Authors:Mirna Lechpammer  Josip Lukač  Stanislav Lechpammer  Dujo Kovačević  Massimo Loda  Zvonko Kusić
Affiliation:(1) Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA;(2) Department of Oncology and Nuclear Medicine, University Hospital Sestre milosrdnice, Vinogradska c. 29, 10000 Zagreb, Croatia;(3) Department of Surgery, University Hospital Sestre milosrdnice, Vinogradska c. 29, 10000 Zagreb, Croatia;(4) Department of Pathology, Brigham and Women"rsquo"s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
Abstract:Background and aims Overexpression of p53 protein in malignancies induces an immune response in some cancer patients. We investigated whether production of serum antibodies against p53 (p53-Ab) is associated with pathohistological parameters of colorectal carcinoma and whether p53-Ab can serve as a tumor marker during cancer treatment.Patients and methods Serum samples from 220 colorectal cancer patients during surgery and adjuvant chemotherapy and 42 healthy controls were tested for the presence of p53-Ab by ELISA. Expression of p53 protein in tumors was determined using mouse anti-human p53-Ab.Results Serum p53-Ab were detected in 18% of patients while all controls were negative. A strong correlation between p53-Ab production and p53 protein expression was observed: 70% of p53-Ab positive cases had tumors positive for p53 vs. 52% of p53-Ab negative cases. There was also a significant predominance of p53-Ab positive cases in Dukesrsquo stages B and C over stage A. Although surgery alone reduced p53-Ab levels, decreases in p53-Ab titer became significant midterm through chemotherapy compared to both pre- and postoperative values and remained decreased until the completion of treatment.Conclusion The presence of p53-Ab in sera of patients with colorectal cancer indicates tumors in more advanced histopathologic stages (Dukesrsquo B, C). Due to low sensitivity (18%) p53-Ab are not recommendable as a preoperative marker for colorectal cancer. However, due to high specificity (100%), their monitoring after surgery and adjuvant chemotherapy has potential for early diagnosis of tumor relapse in p53-Ab positive cases.
Keywords:Colorectal cancer  Tumor suppressor gene p53  Serum p53 antibodies  Cancer treatment  Follow-up
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