Prognostic significance of serum p53 antibodies in patients with limited-stage small cell lung cancer

Zalcman, Gérard; Trédaniel, Jean; Schlichtholz, Beata; Urban, T.; Milleron, B.; Lubin, R.; Meignin, Véronique; Couderc, Louis‐Jean; Hirsch, A; Soussi, Thierry

doi:10.1002/(sici)1097-0215(20000120)89:1<81::aid-ijc13>3.0.co;2-i

Cited by 36 publications

(27 citation statements)

References 16 publications

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“…In addition, the detection of serum anti-p53 Ab is highly specific to cancer. However, the test remains difficult to interpret and conflicting results have arisen from the literature (Murray et al, 2000;Zalcman et al, 2000).…”

Section: à4mentioning

confidence: 99%

CYFRA 21-1 is a prognostic determinant in non-small-cell lung cancer: results of a meta-analysis in 2063 patients

Molinier

Ébert³

et al. 2004

Br J Cancer

165

123

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The purpose of this study was to determine the prognostic significance of a high pretreatment serum CYFRA 21-1 level (a cytokeratin 19 fragment) adjusted for the effects of well-known co-variables in non-small-cell lung cancer (NSCLC). This meta-analysis based on individual updated data gathered comprehensive databases from published or unpublished controlled studies dealing with the prognostic effect of serum CYFRA 21-1 level at presentation in NSCLC of any stage (nine institutions, 2063 patients). Multivariate regression was carried out with the Cox model. The proportional hazard assumption for each of the selected variables retained in the final model was originally checked by log minus log plots baseline hazard ratio. The follow-up ranged from 25 to 78 months. A total of 1616 events were recorded. In the multivariate analysis performed at the 1-year end point, a high pretreatment CYFRA 21-1 level was an unfavourable prognostic determinant in all centres except one (Hazard ratio (95% confidence interval): 1.88 (1.64 -2.15), Po10 À4 ). Other significant variables were stage of the disease, age and performance status. Within the first 18 months, the procedure disclosed a nearly similar hazard ratio for patients having a high pretreatment serum CYFRA 21-1 level (1.62 (1.42 -1.86), Po10 À4 ). For patients who did not undergo surgery, the hazard ratio during the first year of follow-up was 1.78 (1.54 -2.07), Po10À4 . Finally, in the surgically treated population, at the 2-year end point, a high pretreatment CYFRA 21-1 and a locally advanced stage remained unfavourable prognostic determinants. In conclusion CYFRA 21-1 might be regarded as a putative co-variable in analysing NSCLC outcome inasmuch as a high serum level is a significant determinant of poor prognosis whatever the planned treatment.

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Section: à4mentioning

confidence: 99%

CYFRA 21-1 is a prognostic determinant in non-small-cell lung cancer: results of a meta-analysis in 2063 patients

Molinier

Ébert³

et al. 2004

Br J Cancer

165

123

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“…British Journal of Cancer (2000) 83 (11), 1418-1424© 2000 positivity and to avoid possible sampling error, p53-Ab positivity appears to be associated with a longer survival. Dividing the groups into limited and extensive disease, strong p53-Ab positivity was still significant as a predictor for longer survival.…”

Section: Serum P53 Antibodies In Sclc 1421mentioning

confidence: 99%

“…P53 in SCLC has not been studied as extensively, but there are two large studies that we can compare our results with. Work by Zalcman et al (2000) on a French patient cohort from four hospitals in Paris has shown that the presence of p53-Ab, detected with ELISA and IP, bore no relation to survival. The other study by Rosenfeld et al (1997), using only Western blotting, also showed no correlation.…”

Section: Serum P53 Antibodies In Sclc 1421mentioning

confidence: 99%

“…The other study by Rosenfeld et al (1997), using only Western blotting, also showed no correlation. When Zalcman et al (2000) divided their patients into limited and extensive stage, p53-Ab positivity emerged as an independent marker of poor prognosis in limited disease. Table 5 shows the numbers of p53 positive and negative patients with limited stage disease in each of the three studies, indicating a comparable division of patients numbers, all being small, possibly affecting statistical analysis.…”

Section: Serum P53 Antibodies In Sclc 1421mentioning

confidence: 99%

“…There have been two studies looking at p53-Abs in SCLC which have shown a positivity rate for antibodies of the order of 16-20% (Rosenfeld et al, 1997;Zalcman et al, 2000). However, the results of these two studies in relation to patient survival have been contradictory, this being further examined in the discussion.…”

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confidence: 96%

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Serum p53 antibodies: predictors of survival in small-cell lung cancer?

et al. 2000

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Serum p53 antibodies have been shown to be a poor prognostic marker in resected non-small-cell lung cancer (NSCLC), but studies in small-cell lung cancer (SCLC) have been contradictory. We have studied the incidence of p53 antibodies in a large SCLC cohort treated at one oncology centre and correlated the results with survival. 231 patients (63% male, median age 65), diagnosed and treated for SCLC between 1987 and 1994 at The Royal Marsden Hospital NHS Trust, had sera stored pretreatment. All samples were tested for p53 antibodies (p53-Ab) using a standardized ELISA technique with a selection of strongly ELISA positive, weakly ELISA positive and negative samples being confirmed with immunoprecipitation. 54 patients were positive for p53-Ab (23%). The presence of a high titre of p53-Ab (titre ratio >5) appears to be associated with a survival advantage with a relative risk of death of 1.71 (95% CI: 1.14–2.58) in those without the antibody (P = 0.02). This study, the largest homogenous group so far looking at p53-Ab in SCLC, suggests that p53 antibody detection may have a role in predicting outcome in this type of cancer. © 2000 Cancer Research Campaign http://www.bjcancer.com

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Toward a more complete recognition of immunoreactive antigens in squamous cell lung carcinoma

Diesinger

Bauer

Brass

et al. 2002

Intl Journal of Cancer

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There is very limited knowledge about the antibody response against tumor-expressed antigens in lung cancer. To arrive at a more complete picture of lung cancer antigens, we generated 2 cDNA libraries from squamous cell lung carcinoma and isolated 15 immunogenic antigens using autologous sera. Among the antigens most frequently identified were the lymphoid blast crisis oncogene (LBC), an unknown hypothetical protein and the p53-binding protein (TP53 BP), which have already been associated with tumor development. Of the immunogenic antigens, 6 map to chromosomes that are frequently altered in squamous cell lung carcinoma. SEREX database analysis showed that 7 of the identified immunogenic antigens have been associated with the humoral immune response in other human tumors. Screening with heterologous sera of patients with lung carcinoma identified 4 antigens, including human protein kinase C and TP53 BP, which have also been found by autologous screening. Only 1 of the 15 identified antigens reacted with any of the 36 control sera, which were taken from individuals without known disease. Sera from adenocarcinoma and large cell carcinoma of the lung were not reactive for the antigens. In summary, using 2 newly established cDNA libraries, we isolated 15 novel antigens, which were subsequently evaluated for the frequency of their corresponding antibodies in autologous, normal and heterologous sera; their chromosomal localization; and their correlation with survival after surgery. © 2002 Wiley-Liss, Inc. Key words: lung cancer; SEREX; autologous sera; heterologous seraThere is mounting evidence that many tumors express antigens that elicit an immune response in cancer patients. Target antigens of tumor-related autoantibodies can be oncoproteins, tumor-suppressor proteins or proliferation-associated antigens. 1 The most prominent example of an autoimmune response against a tumorassociated protein is the antibody response against the tumorsuppressor TP53. Examples of TP53-directed antibodies in cancer patients include antibodies in 50% of bladder cancer patients, in 12% of B-cell lymphoma patients, in 23% of ovarian cancer patients, in 32% of colon cancer patients and in 42% of breast cancer patients. [2][3][4][5][6] In addition, there is an increasing number of other tumor or proliferation-associated gene products that cause an antibody response, including, e.g., c-myb with an antibody response in 43% of breast cancer patients and cyclin B1 in 15% of hepatocellular carcinoma patients. 7,8 There are limited data on the autoantibody response in human lung cancer patients, specifically patients suffering from squamous cell lung carcinoma, which constitutes 40 -50% of lung cancer patients. Lung cancer is the most frequent lethal tumor in Western societies, with a 5-year survival rate of approximately 13%. 9 The most frequent autoantibodies in lung cancer patients are directed against TP53, with an antibody response detected in 14.3% of lung cancer patients and 21% of small cell lung cancer patients, and against L-myc and ...

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Prognostic significance of serum p53 antibodies in patients with limited-stage small cell lung cancer

Cited by 36 publications

References 16 publications

CYFRA 21-1 is a prognostic determinant in non-small-cell lung cancer: results of a meta-analysis in 2063 patients

CYFRA 21-1 is a prognostic determinant in non-small-cell lung cancer: results of a meta-analysis in 2063 patients

Serum p53 antibodies: predictors of survival in small-cell lung cancer?

Toward a more complete recognition of immunoreactive antigens in squamous cell lung carcinoma

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