The value of serum p53 antibody as a biomarker in oral and pharyngeal squamous cell carcinoma.

BACKGROUND: The development of more sensitive biomarkers for the detection of early-stage head and neck squamous cell carcinoma is needed. AIMS/OBJECTIVES: This study was performed to assess the value of serum p53 antibody (s-p53-Ab) as a biomarker for oral and pharyngeal carcinoma. MATERIAL AND METHODS: Pre-treatment serum was collected for 71 patients with oral and pharyngeal carcinoma and 117 healthy volunteers as controls and analyzed s-p53-Ab using enzyme-linked immunosorbent assay (ELISA). RESULTS: Using 1.3 U/mL as the cut-off value, 14 of 71 patients (sensitivity 19.7%), and 12 of 117 control cases were positive for s-p53-Ab (specificity 89.7%). Excluding 12 cases of p16-positive oropharyngeal and nasopharyngeal cancer which were all negative for s-p53-Ab, the sensitivity in early-stage 1-2 cases was 30.0%, which was higher than conventional tumor markers. CONCLUSIONS AND SIGNIFICANCE: The s-p53-Ab was not detected in any cases of virus-related cancer in which p53 gene mutations were not involved in carcinogenesis. Since the s-p53-Ab sensitivity was high even in early-stage disease, s-p53-Ab measurement may be useful as an early diagnostic biomarker in patients with oral, p16- oropharyngeal, and hypopharyngeal cancer.

Comparison between a new assay system, Elecsys® Anti-p53, and conventional MESACUP™ for the detection of serum anti-p53 antibodies: A multi-institutional study.

The sensitivity and specificity of a new automated electrochemiluminescence immunoassay system, Elecsys® Anti-p53 (Elecsys), were compared with that of the conventional serum anti-p53 antibody (s-p53-Ab) enzyme-linked immunosorbent assay kit [MESACUP anti-p53 test (MESACUP)]. Elecsys and MESACUP were used to analyze the levels of s-p53-Abs in patients with esophageal, colorectal and breast cancer. A total of 532 controls and 288, 235 and 329 patients with esophageal, colorectal and breast cancer, respectively, were enrolled. Additionally, the sera of patients with benign diseases of the esophagus, colorectal system and breast, patients with autoimmune diseases and healthy volunteers were analyzed as controls. Sensitivity and specificity were compared between the two assay systems. Positive agreement rates were 58.7% in all samples, 71.2% in esophageal samples, 73.6% in colorectal samples and 35.1% in breast samples. Negative agreement rates for the different cancer types were ≥97.1% and the overall agreement rates were ≥92.3%. When the specificities of the two assays were aligned for all samples, Elecsys demonstrated higher sensitivities for all types of analyzed cancer together, as well as for esophageal, colorectal and breast cancer, respectively. Although positive concordance between the two assay systems was low in terms of specificity, Elecsys had a higher sensitivity than the MESACUP.

Re-evaluating the clinical significance of serum p53 antibody levels in patients with oral cancer in Japanese clinical practice.

TP53 gene mutations can lead to mutant p53 protein accumulation in cancer cells, thereby inducing the production of serum antip53 antibodies (Ap53Ab) in patients with various types of cancer. The aim of the present study was to re-evaluate the clinicopathological and prognostic significance of Ap53Ab using the Ap53Ab ELISA kit, approved by the Japanese Health Insurance System in 2007. Ap53Ab was measured as a tumor marker in 94 patients with oral squamous cell carcinoma (OSCC), by subjecting paraffin-embedded sections obtained from biopsy specimens to immunohistochemical analysis to confirm p53 expression. The associations among Ap53Ab status, p53 expression and clinical significance in OSCC were examined. A total of 23% of the patients were Ap53Ab-positive. Ap53Ab status was found to be significantly associated with p53 expression status in primary tumors (P=0.027), clinical T-category, pathological N-category and pathological stage (P=0.04, P=0.010 and P=0.013, respectively). Kaplan-Meier curve analysis revealed that Ap53Ab status was significantly associated with poor disease-free survival (DFS; P=0.043), and Cox regression analysis revealed that Ap53Ab status was a significant prognostic factor for DFS in patients with OSCC (hazard ratio=2.807; 95% confidence interval: 1.029-7.160; P=0.044). These results suggested that Ap53Ab measurement may reflect the p53 mutation status and an aggressive malignant phenotype, and it may serve as a useful predictive marker candidate for OSCC in clinical practice.

Serum p53 antibody: useful for detecting gastric cancer but not for predicting prognosis after surgery.

PURPOSE: To establish the clinicopathological importance of serum p53 autoantibody (s-p53-Ab) titrations in patients with gastric cancer. METHODS: Preoperative s-p53-Ab titers were analyzed in 448 gastric cancer patients between 2010 and 2017. Seropositive patients were divided into three groups based on their antibody titers: 1.31-10.0 U/mL (low group); 10.1-100 U/mL (medium group); and > 100 U/mL (high group). We evaluated the associations between the s-p53-Abs and clinicopathological factors, carcinoembryonic antigen (CEA) levels, and cancer antigen 19-9 (CA19-9) levels. Overall survival was analyzed by multivariate analyses. RESULTS: A total of 72 patients (16%) were positive for s-p53-Abs. The rate of positivity for s-p53-Abs + CEA + CA19-9 was significantly higher than that for CEA + CA19-9, even in stage I gastric cancers. Gender, tumor depth, lymphatic node metastases, and distant metastases were all significantly associated with the presence of s-p53-Abs; however, overall survival was not associated with the antibodies. The patients in the high titer group (> 100 U/mL) had a relatively worse survival than those in the other groups. CONCLUSIONS: Based on our findings, s-p53-Abs improve the overall rate of positivity for detecting gastric cancer, but the prognostic value of a high s-p53-Ab titer for predicting overall survival is limited.

Changing pattern of tumor markers in recurrent colorectal cancer patients before surgery to recurrence: serum p53 antibodies, CA19-9 and CEA.

BACKGROUND: The clinical impact of monitoring serum p53 antibodies, carbohydrate antigen19-9, and carcinoembryonic antigen in patients with colorectal cancer has not been fully evaluated. METHODS: A total of 420 surgically treated stage II/III colorectal cancer patients were retrospectively analyzed. Among them, 101 patients developed disease recurrence. The prognostic impact of preoperative and recurrence levels of serum p53 antibodies, carbohydrate antigen19-9, and carcinoembryonic antigen status was evaluated. RESULTS: Although preoperative carcinoembryonic antigen- and carbohydrate antigen19-9-positive status was significantly associated with recurrence, preoperative serum p53 antibody levels were not. Among two marker combinations, carcinoembryonic antigen + serum p53 antibodies showed the highest positive rate at recurrence. Although carcinoembryonic antigen and carbohydrate antigen19-9 frequently converted from preoperative-negative status to positive status at recurrence, serum p53 antibodies converted to positive status in only one patient. Carcinoembryonic antigen- and carbohydrate antigen19-9-positive status were significant prognostic factors for overall survival after recurrence, but the presence of serum p53 antibodies at recurrence was not. CONCLUSIONS: Postoperative serum p53 antibody status should only be followed in patients with preoperative-positive status. Carcinoembryonic antigen and carbohydrate antigen19-9 should be followed even in preoperative-negative patients. Unlike carcinoembryonic antigen- and carbohydrate antigen19-9-positive status, serum p53 antibody-positive status as recurrence was not a poor prognostic indicator.

Prognostic significance of high serum p53 antibody titers in patients with esophageal squamous cell carcinoma.

BACKGROUND: The p53 protein overexpression that usually results from genetic alterations reportedly induces serum antibodies against p53. However, little information is available about the prognostic significance of perioperative serum p53 antibody (s-p53-Abs) titers in patients with esophageal squamous cell carcinoma. METHODS: In this study, we retrospectively evaluated the clinical significance of perioperative s-p53-Abs in 135 patients with esophageal squamous cell carcinoma. Of these, 58 patients received neoadjuvant chemotherapy comprising 5-FU and CDDP. While the cutoff level at 1.3 U/ml indicated seropositive patients, level of 13.4 U/ml was used to identify high-titer patients. We monitored serum titers seropositive patients after surgery and evaluated the prognostic significance by the univariate and multivariate analyses. RESULTS: In this study, 29 patients (21.5%) were positive for s-p53-Abs before treatment. The frequency of both seropositive patients and high-titer patients (> 13.4 U/ml) was not significantly associated with tumor progression. While seropositive patients did not demonstrate significant poor overall survival, high-titer patients demonstrated significant poor overall survival based on the multivariate analysis (P < 0.001). Moreover, the s-p53-Abs titer did not correlate with the response to neoadjuvant chemotherapy. Among seropositive patients, the negative conversion of s-p53-Abs more likely led to be long-term survival. CONCLUSIONS: This study determined that the high-titer of s-p53-Abs was an independent risk factor to reduce the overall survival of patients with esophageal cancer patients. The negative conversion of s-p53-Abs could be a good indicator of favorable prognosis.

Potential diagnostic value of serum p53 antibody for detecting colorectal cancer: A meta-analysis.

Numerous studies have assessed the diagnostic value of serum p53 (s-p53) antibody in patients with colorectal cancer (CRC); however, results remain controversial. The present study aimed to comprehensively and quantitatively summarize the potential diagnostic value of s-p53 antibody in CRC. The present study utilized databases, including PubMed and EmBase, systematically regarding s-p53 antibody diagnosis in CRC, accessed on and prior to 31 July 2016. The quality of all the included studies was assessed using quality assessment of studies of diagnostic accuracy (QUADAS). The result of pooled sensitivity, pooled specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were analyzed and compared with overall accuracy measures using diagnostic odds ratios (DORs) and area under the curve (AUC) analysis. Publication bias and heterogeneity were also assessed. A total of 11 trials that enrolled a combined 3,392 participants were included in the meta-analysis. Approximately 72.73% (8/11) of the included studies were of high quality (QUADAS score >7), and all were retrospective case-control studies. The pooled sensitivity was 0.19 [95% confidence interval (CI), 0.18-0.21] and pooled specificity was 0.93 (95% CI, 0.92-0.94). Results also demonstrated a PLR of 4.56 (95% CI, 3.27-6.34), NLR of 0.78 (95% CI, 0.71-0.85) and DOR of 6.70 (95% CI, 4.59-9.76). The symmetrical summary receiver operating characteristic curve was 0.73. Furthermore, no evidence of publication bias or heterogeneity was observed in the meta-analysis. Meta-analysis data indicated that s-p53 antibody possesses potential diagnostic value for CRC. However, discrimination power was somewhat limited due to the low sensitivity.

Clinical Value of Serum p53 Antibody in the Diagnosis and Prognosis of Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: Identifying useful biomarkers is central to selecting optimal therapeutic strategies for esophageal squamous cell carcinoma (ESCC). Serum p53 antibody (S-p53Ab), squamous cell carcinoma antigen (SCC-Ag), and carcinoembryonic antigen (CEA) were investigated to evaluate the significance of single and combined tumor markers in determining the diagnosis and prognosis of ESCC. MATERIALS AND METHODS: Serum samples were obtained preoperatively from 133 patients with histologically-confirmed ESCC, including 32 patients with stage I (24.1%). Levels of S-p53Ab were assessed by enzyme-linked immunosorbent assay, using a new version of a highly specific, quantitative kit. The cut-off value for S-p53Ab was 1.3 U/ml. RESULTS: S-p53Ab was detected in 39.1% (52 out of 133) of patients with ESCC, including 40.0% (20 out of 50) of patients with early-stage ESCC. Positive rates for S-p53Ab, CEA, and SCC-Ag among patients with stage I ESCC (n=32) were 40.6%, 12.5%, and 31.3%, respectively. Positivity for S-p53Ab was not associated with positivity for CEA or SCC-Ag (p=0.249 and 0.747, respectively). The positive rate for diagnosis of ESCC increased from 39.1% to 65.4% when S-p53Ab was combined with SCC-Ag in this study. We found no significant correlation between the presence of S-p53Ab in ESCC and overall survival. Conversely, Cox regression analysis revealed that the International Union Against Cancer/TNM classification and systemic inflammation score were independent prognostic factors for ESCC in this series (hazard ratio(HR)=3.811, 95% confidence interval(CI)=1.548-9.378, p=0.004; and HR=2.218; 95% CI=1.087-4.523, p=0.029, respectively). Kaplan-Meier analysis revealed significant differences between patients with elevated S-p53Ab and SCC-Ag and patients with elevated levels of only one or neither of these factors (p=0.009). CONCLUSION: The diagnostic rate with S-p53Ab was better than that with SCC-Ag and CEA in patients with early-stage ESCC. Combined detection of S-p53Ab and SCC-Ag can markedly improve diagnostic sensitivity and may permit more accurate stratification of patients with ESCC.

Five-year postsurgical monitoring of serum p53 antibody for locally advanced esophageal squamous cell carcinoma.

Serum p53 antibody (s-p53-Ab) titers were postoperatively monitored for over 5 years in a 67-year-old man with locally advanced esophageal squamous cell carcinoma. The tumor stage was classified as clinical stage II (cT3N0M0). Serum SCC antigen (s-SCC-Ag; 6.2 ng/mL) and s-p53-Ab (3.83 U/mL) were noted to be positive before surgery. Radical esophagectomy with three-field lymph node dissection was performed without neoadjuvant therapy. Pathological findings of the surgically resected specimens revealed a stage II tumor (pT3N0M0). Postoperatively, the patients did not receive any adjuvant therapy. Although the s-SCC-Ag was found to be negative at 2 months postoperatively, s-SCC-Ag was found to be six times positive despite no signs of recurrence. The s-p53-Ab titers constantly decreased to less than the cutoff value at 6 months postoperatively and continuously decreased over 5 years postoperatively. Finally, s-p53-Ab titers became less than the detection limit value at 60 months postoperatively. No recurrence was observed throughout the postoperative course. This case report is the first to describe the five-year monitoring of postoperative changes in s-p53-Ab titers in a patient with locally advanced esophageal squamous cell carcinoma without recurrence. s-p53-Ab titers seemed to be more useful than s-SCC-Ag for disease monitoring in this case.

Negative conversion of high serum p53 antibody titers in a patient with gastric cancer at 31 months after surgery.

We performed distal gastrectomy with D2 lymph node dissection, pathological stage was Stage IB (T2N0M0), in a 68-year-old male with gastric adenocarcinoma. We then monitored serum p53 antibody titers for 5 years and found it consistently decreased, without disease recurrence. Although the s-p53-Ab titer remained positive even after 2 years, it decreased to 16.5, 4.45, 2.66, 1.55, and 1.18 U/ml at 3 months, 7 months, 1 year, 2 years and 3 years after surgery, respectively. The s-p53-Ab titer finally converted from positive to negative at 31 months postoperatively without any sign of recurrence by computed tomography examination at 5 years after surgery. This case report shows that the changing pattern of s-p53-Ab titer after surgery may be useful to identify patients without recurrence. Further studies are required to gain a more precise understanding of the clinical impact of s-p53-Ab titer monitoring in gastric adenocarcinoma.

Clinical Significance of Serum p53 Antibody in the Early Detection and Poor Prognosis of Gastric Cancer.

BACKGROUND: The aim of this retrospective study was to evaluate the clinical relevance of serum p53 antibody (S-p53Ab) as a biomarker and to investigate whether its diagnostic value could be improved when combined with other biomarkers of gastric cancer (GC). PATIENTS AND METHODS: Serum samples were obtained preoperatively from 208 patients with histologically-confirmed GC, including 126 stage I patients (60.6%). Levels of S-p53Ab were assessed by a commercial laboratory using an anti-p53 detection kit. The cut-off value for S-p53Ab was 1.3 U/ml. RESULTS: S-p53Ab was detected in 16.3% (34 of 208) of patients with GC, including 13.6% (22 of 162) of patients with early-stage GC. The positive rates for S-p53Ab, carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) of patients with stage I GC were 10.3% (13/126), 2.4% (3/126), and 8.7% (11/126), respectively. Positivity for S-p53Ab was not associated with CA19-9 or CEA positivity (p=0.098 and 0.053, respectively). The positive rate for a diagnosis of GC increased from 16.3% to 29.3% when S-p53-Ab was combined with CEA in this study. We found no significant correlation between the presence of S-p53Ab in GC and overall survival. Conversely, Cox regression analysis revealed that a high level of CA19-9 was an independent prognostic factor for GC in this series (hazard ratio(HR)=3.864; 95% confidence interval(CI)= 1.248-11.959; p=0.019). Kaplan-Meier analyses demonstrated significant differences in survival between patients with elevated levels of both S-p53Ab and CEA and those with elevated levels of only one or neither. CONCLUSION: The diagnostic rate of S-p53Ab was better than that of CA19-9 and CEA in patients with stage I GC. Combined detection of S-p53Ab and CEA may improve the diagnostic sensitivity and may permit more accurate stratification of GC patients.

The utility of tumor marker combination, including serum P53 antibody, in colorectal cancer treatment.

PURPOSES: Serum P53 antibody (S-P53Ab) is reportedly an effective screening tool for cancer. The aim of this study is to investigate the clinical significance of tumor markers combination in colorectal cancer (CRC) patients. METHODS: Carcinoembryonic antigen (CEA), carbohydrate 19 - 9 (CA19-9), and S-P53Ab levels were measured before tumor resection. Of the CRC patients with primary tumor resection at Kumamoto University Hospital, a total of 244 with available preoperative data for these three tumor markers were eligible for this study. The associations of the tumor markers with clinicopathological factors and the prognosis were examined using univariate and multivariate analyses. RESULTS: S-P53Ab positivity was strongly correlated with rectal cancer, depth of tumor invasion, lymph node metastasis, and lymphatic invasion. The ratio of S-P53Ab positivity was higher than that of CEA or CA19-9 in patients with stage 0/I disease. S-P53Ab had no power to predict the prognosis (P = 0.786). The patients with combined CEA and CA19-9 positivity had a significantly poorer overall survival than those with positivity for neither or only one, and combined CEA and CA19-9 positivity was an exclusive independent prognostic factor (P = 0.034). CONCLUSIONS: The clinical significance of S-P53Ab measurement in CRC patients is limited. However, the combination of CEA and CA19-9 levels may be effective for predicting the outcomes of CRC treatment.

Clinical Value of Serum p53 Antibody in the Diagnosis and Prognosis of Colorectal Cancer.

BACKGROUND: Serum p53 antibody (s-p53Ab), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) were investigated to evaluate the significance of these singly and combined tumor markers in the diagnosis and prognosis of colorectal cancer (CRC). PATIENTS AND METHODS: Preoperative serum samples were obtained from 170 patients with histologically confirmed CRC, including 28 (16%) with stage I. s-p53Ab was assessed using the MESACUP Kit II, that is a new and highly specific version of a quantitative p53-Abs enzyme-linked immunosorbent assay. RESULTS: s-p53Ab was detected in 30.6% (52 out of 170) of patients with CRC, including 31.9% (29/91) of patients with early-stage CRC. The positive rates for CEA and CA19-9 of patients with CRC were 28.8% (49/170) and 22.9% (39/170), respectively. Combining use of s-p53-Ab with CEA increased the positive rate of a diagnosis of CRC to 48.8%. Positivity for s-p53Ab in CRC did not correlate with overall survival. On the other hand, Cox regression analysis of this series revealed that high levels of CEA served as an independent prognostic factor for CRC. Kaplan-Meier analysis revealed significant differences between patients with elevated s-p53Ab and CEA and those with elevated levels of either one or neither of these factors (p<0.001). CONCLUSION: The diagnostic rate of s-p53Ab was better than that of CEA and CA19-9 in patients with early-stage CRC. Combined detection of s-p53Ab and CEA can improve diagnostic sensitivity and may permit more accurate stratification of patients with CRC.

Three-year monitoring of serum p53 antibody during chemotherapy and surgery for stage IV rectal cancer.

The overexpression of mutant p53 stimulates serum p53 antibody production in patients with colorectal carcinoma even in superficial tumors. Although the short-term perioperative monitoring of serum p53 antibody titers is reported to be useful in predicting tumor recurrence and patient survival in colorectal carcinoma, the clinical utility of the long-term monitoring of serum p53 antibody titers in patients with colorectal cancer remains unknown. Here, we report the 3-year monitoring of serum p53 antibody titers in a 60-year-old man with rectal cancer, clinical stage IV (T2N2M1b, lung and liver metastases), who was treated with chemotherapy and surgery. Screening tests for CEA (29.4 ng/ml), CA19-9 (41.1 U/ml), and serum p53 antibody (2170 U/ml) were positive before treatment. After chemotherapy with mFOLFOX6 + bevacizumab (B-mab), CEA and CA19-9 decreased to the normal range. However, serum p53 antibody titer remained positive (283 U/ml). After low anterior resection, the serum p53 antibody titer still remained positive (63.4 U/ml). Serum p53 antibody titer significantly changed and was associated with treatment response and tumor recurrence. In the last 6 months of the patient's life, serum p53 antibody titer gradually decreased, which possibly reflects the modification of the patient's immune response to p53 antigens.

Normalization of serum p53 antibody levels in patients after curative resection for colorectal cancer.

BACKGROUND: The aim of this study was to evaluate the significance of high serum p53 antibody (p53Ab) levels in relation to curative resection of colorectal cancer. PATIENTS AND METHODS: Between 2007 and 2010, 24 patients with colorectal cancer with higher-than-normal preoperative serum p53Ab, measured by enzyme-linked immunosorbent assay, were enrolled in this study. After curative resection, their serum p53Ab and carcinoembryonic antigen (CEA) levels were measured at one, six, 12, 18, and 24 months after surgery. The relationship between clinicopathological features and the presence of serum p53Ab was evaluated. RESULTS: None of the patients developed recurrence up to 24 months after the surgery. The positive rate for CEA was 33.3% before surgery, 16.7% at one month after surgery, and 0% at six months and more, while the rate for p53Ab was 75% at six months, 70.8% at 12 months, 58.3% at 18 months, and 54.2% at 24 months after surgery. The positive rate for serum p53Ab at 24 months after the surgery correlated with the one before and that at one month after the surgery. CONCLUSION: For patients with colorectal cancer and high preoperative serum p53Ab levels, serum p53Ab does not seem to be a useful marker of recurrence after curative resection, since normalization of serum p53Ab levels requires years after surgery.