Clinical Implications of p53 Autoantibodies in the Sera of Patients With Non-Small-Cell Lung Cancer

Mitsudomi, Tetsuya; Hatooka, Shunzo; Sekiguchi, Masayuki; Suyama, Motokazu; Yatabe, Yasushi; Kuwabara, Masaki; Nishio, Masayuki; Gotoh, Kunihiko; Ogawa, Makoto; Takahashi, Toshitada; Takahashi, Takashi; Suzuki, Susumu; Ariyoshi, Y

doi:10.1093/jnci/90.20.1563

Cited by 46 publications

(31 citation statements)

References 12 publications

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“…For example, antibodies to NY-ESO-1 are found in ≈50% of stage IV melanoma patients expressing NY-ESO-1 in their tumor, but the overall frequency in melanoma is about 8% when considering earlier stages (with less frequent NY-ESO-1 expression) and nonexpressing tumors (31). Similarly, p53 and XAGE-1 are immunogenic in 10-30% of non-small-cell lung cancers, depending on type and stage, but very rarely so in melanoma (35)(36)(37). Therefore, in the current study, the frequencies of seroreactivity observed against top antigens in pancreatic and ovarian cancer patients have to be placed in the context of cognate antigen expression frequency, tumor type selected, and stage.…”

Section: Discussionmentioning

confidence: 99%

Seromic profiling of ovarian and pancreatic cancer

Gnjatic

Ritter

Büchler³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

163

142

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Autoantibodies, a hallmark of both autoimmunity and cancer, represent an easily accessible surrogate for measuring adaptive immune responses to cancer. Sera can now be assayed for reactivity against thousands of proteins using microarrays, but there is no agreed-upon standard to analyze results. We developed a set of tailored quality control and normalization procedures based on ELISA validation to allow patient comparisons and determination of individual cutoffs for specificity and sensitivity. Sera from 60 patients with pancreatic cancer, 51 patients with ovarian cancer, and 53 age-matched healthy donors were used to assess the binding of IgG antibodies against a panel of >8000 human antigens using protein microarrays and fluorescence detection. The resulting data interpretation led to the definition and ranking of proteins with preferred recognition by the sera from cancer patients in comparison with healthy donors, both by frequency and strength of signal. We found that 202 proteins were preferentially immunogenic in ovarian cancer sera compared to 29 in pancreatic cancer, with few overlaps. Correlates of autoantibody signatures with known tumor expression of corresponding antigens, functional pathways, clinical stage, and outcome were examined. Serological analysis of arrays displaying the complete human proteome (seromics) represents a new era in cancer immunology, opening the way to defining the repertoire of the humoral immune response to cancer. serum antibody | biomarkers | protein microarrays | serology | autoantigen

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Section: Discussionmentioning

confidence: 99%

Seromic profiling of ovarian and pancreatic cancer

Gnjatic

Ritter

Büchler³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

163

142

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“…The presence of p53-Ab, often reflecting p53 mutation, has been associated with poor prognosis and shorter survival in NSCLC (Quinlan et al, 1992;Marchetti et al, 1993;Harpole et al, 1995;Laudanski et al, 1998). Some groups have found no such correlation (McLaren et al, 1992;Mitsudomi et al, 1998) and others have shown a favourable prognosis (Lee et al, 1995;Bergqvist et al, 1998). P53 in SCLC has not been studied as extensively, but there are two large studies that we can compare our results with.…”

Section: Serum P53 Antibodies In Sclc 1421mentioning

confidence: 99%

“…Most recently p53 mutations detectable in tumour samples have been shown to be not only an independent marker for poor outcome in resectable stage I NSCLC (Harpole, 1995), but also to correlate with nodal involvement and thus shorter survival (Marchetti et al, 1993). In NSCLC there is a prevalence of p53 antibodies of around 24% correlated with a much higher rate of p53 mutation, of the order of 60-70% (Schlichtholz et al, 1992;Winter et al, 1992;Wild et al, 1995;Komiya et al, 1997;Rosenfeld et al, 1997;Bergqvist et al, 1998;Iizasa et al, 1998;Laudanski et al, 1998;Mitsudomi et al, 1998;Segawa et al, 1998). Studies have shown a decrease in levels of p53-Abs in patients treated for lung cancer (Zalcman et al, 1998).…”

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confidence: 99%

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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“…The presence of anti-p53 antibodies has been frequently found in the sera of patients with lung cancer containing p53 mutations (Iizasa et al, 1998). In a study with 188 patients with NSCLC, anti-p53 antibodies were detected in over 20% of the patients although it is more frequently detected in patients with more advanced disease (Mitsudomi et al, 1998). Several other auto-antibodies have recently been identi®ed as potential biomarkers in lung cancer detection.…”

Section: Detect Molecular Changes In Bloodmentioning

confidence: 99%

Recent advances in the molecular diagnosis of lung cancer

2002

Oncogene

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Clinical Implications of p53 Autoantibodies in the Sera of Patients With Non-Small-Cell Lung Cancer

Abstract: In NSCLC, the incidence of p53 autoantibodies is associated with histologic type, stage, and p53 overexpression--but not with patient survival. Our data do not support the clinical utility of p53 autoantibodies as diagnostic or prognostic markers in patients with NSCLC.

Cited by 46 publications

References 12 publications

Seromic profiling of ovarian and pancreatic cancer

Seromic profiling of ovarian and pancreatic cancer

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

Recent advances in the molecular diagnosis of lung cancer

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