RESUMEN
BACKGROUND: Despite evidence suggesting a role of chronic pancreatitis in pancreatic carcinogenesis, its relationship with invasive intraductal papillary mucinous neoplasms (IPMN) remains unclear. Low levels of pancreatic enzymes are predictive markers of advanced chronic pancreatitis. We investigated whether low pancreatic enzyme levels were associated with a higher incidence of invasive IPMN. METHODS: This study included 146 consecutive patients who underwent surgical resection of IPMN between April 2001 and October 2014. Multivariable logistic regression analysis was conducted to assess the association between serum pancreatic enzymes and the incidence of invasive IPMN, with adjustment for clinical characteristics including alcohol consumption. The association of serum pancreatic enzymes with pathological pancreatic atrophy and inflammation in areas adjacent to or distant from the tumor was also evaluated. RESULTS: Low serum levels of pancreatic amylase and lipase were associated with a higher incidence of invasive IPMN (multivariable odds ratio [OR] = 9.6, 95% confidence interval [CI] = 2.99 to 35.1, P = 0.0001; OR = 14.2, 95% CI = 2.77 to 112, P = 0.001, respectively). Low serum pancreatic amylase and lipase levels were also associated with higher grade pancreatic atrophy in areas adjacent to the tumor (P = 0.011 and P = 0.017, respectively) and in areas distant from the tumor (P = 0.0002 and P = 0.001, respectively). Furthermore, low serum pancreatic amylase and lipase levels were associated with higher grade inflammation in areas distant from the tumor (P < 0.0001 and P = 0.001, respectively). CONCLUSIONS: Low serum pancreatic enzymes may be a predictive marker of invasive IPMN. Excessive alcohol consumption did not influence the association of low pancreatic enzyme levels with invasive IPMN.
Asunto(s)
Páncreas/enzimología , Neoplasias Pancreáticas/enzimología , Papiloma Intraductal/enzimología , Adulto , Anciano , Consumo de Bebidas Alcohólicas , Amilasas/sangre , Atrofia , Calcinosis/enzimología , Femenino , Humanos , Lipasa/sangre , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Páncreas/patología , Páncreas/cirugía , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Pancreatitis/enzimología , Pancreatitis/patología , Papiloma Intraductal/diagnóstico por imagen , Papiloma Intraductal/cirugía , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
Cyclooxygenase-2 (COX-2) is reported to play an important role in carcinogenesis. We examined COX-2 expression in patients with breast cancer and benign breast tumors. Immunohistochemical staining revealed a high level of COX-2 expression in malignant lesions of invasive ductal carcinoma (IDC) at a rate of 40% and a low level of expression in 15% of adjacent normal-appearing breast epithelia. Similarly, in ductal carcinoma in situ (DCIS), a high level of COX-2 expression was found in 80% of malignant lesions and a low level of expression in 50% of normal epithelia. Reverse transcriptional polymerase chain reaction (RT-PCR) performed in 7 of these cases disclosed that COX-2 expression was restricted to the malignant lesion. Further, all 10 cases of fibroadenoma and 10 cases of intraductal papilloma, both of which are benign tumors, had a high level of COX-2 expression. When overexpression of COX-2 was analyzed in relation to the clinicopathological features of the patients, no characteristic correlation was noted. Our results demonstrated that COX-2 is expressed in mammary tissue during tumorigenesis of the breast gland, suggesting that the cyclooxygenase isoenzyme may be a target for the prevention and treatment of breast cancer.
Asunto(s)
Neoplasias de la Mama/enzimología , Isoenzimas/biosíntesis , Prostaglandina-Endoperóxido Sintasas/biosíntesis , Neoplasias de la Mama/patología , Carcinoma in Situ/enzimología , Carcinoma Ductal de Mama/enzimología , Ciclooxigenasa 2 , Femenino , Fibroadenoma/enzimología , Humanos , Inmunohistoquímica , Proteínas de la Membrana , Papiloma Intraductal/enzimología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF) have been reported to be significantly related to carcinogenesis or progression of various cancers. However, there has been no report on the relation between COX-2 and VEGF overexpression in pancreatic tumors. We investigated the overexpression of COX-2 and VEGF immunohistochemically in intraductal papillary-mucinous tumors (IPMT) and invasive ductal carcinoma (IDC) and examined the relationship with clinicopathological factors and the correlation between these immunoactivities in IPMT and IDC. In IPMT, the positive rates of COX-2 overexpression were 0% in 10 areas of hyperplasia, 54.5% of adenoma, 83.3% of intraductal areas of adenocarcinoma, and 66.7% of invasive areas of adenocarcinoma. On the contrary, 47.8% of IDC were positive for COX-2 overexpression. The positive rates of VEGF in IPMT were 10% in areas of hyperplasia, 54.5% of adenoma, 66.7% of intraductal areas of adenocarcinoma and 66.7% of invasive areas of adenocarcinoma. However, in IDC it was 47.8%. Only lymph node metastasis correlated significantly with VEGF overexpression (p=0.04), while the other factors had no significant relationships with either COX-2 or VEGF overexpression. There was a statistically significant correlation between COX-2 and VEGF overexpression in IPMT (p<0.001), in 5 patients with adenoma of which both COX-2 and VEGF were stained in almost exactly the same locations. On the contrary, COX-2 and VEGF overexpression had no statistically significant relationship in IDC. In conclusion, we demonstrate evidence of COX-2 and VEGF overexpression in human pancreatic tumors. Chemoprevention via the suppression of angiogenesis by means of COX-2 inhibitor may be more effective in IPMT than in IDC, because of the strong correlation of both factors especially in IPMT.
Asunto(s)
Factores de Crecimiento Endotelial/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Isoenzimas/metabolismo , Linfocinas/metabolismo , Neoplasias Pancreáticas/enzimología , Prostaglandina-Endoperóxido Sintasas/metabolismo , Adenocarcinoma/enzimología , Adenocarcinoma/patología , Adenocarcinoma Mucinoso/enzimología , Adenocarcinoma Mucinoso/patología , Adenoma/enzimología , Adenoma/patología , Carcinoma Ductal Pancreático/enzimología , Carcinoma Ductal Pancreático/patología , Ciclooxigenasa 2 , Humanos , Técnicas para Inmunoenzimas , Metástasis Linfática , Proteínas de la Membrana , Invasividad Neoplásica , Neoplasias Pancreáticas/patología , Papiloma Intraductal/enzimología , Papiloma Intraductal/patología , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
BACKGROUND: The diagnosis of breast cancer based on nipple discharge, often the only clinical manifestation of early breast cancer, is currently unsatisfactory. Because M subunits of lactate dehydrogenase (LDH) have been noted to increase in cancer tissue, the author assessed the value of using LDH isozyme patterns in nipple discharge for the diagnosis of breast cancer. METHODS: LDH isozyme levels in (1) nipple discharge of patients diagnosed as having breast cancer, intraductal papilloma, mastopathy, drug-induced nipple discharge, mastitis, or benign nipple discharge; (2) control samples of normal nipple discharge (milk) 6 days, 1-5 months, and 6 months to 2 years postpartum; (3) the serum of patients presenting with nipple discharge; and (4) normal and cancerous breast tissue extracts were measured using a Ciba-Corning LDH isozyme system (Ciba Corning Diagnostic Corp., Tokyo, Japan). RESULTS: LDH isozyme levels in the nipple discharge of patients with benign breast diseases displayed various patterns. Levels in the nipple discharge of patients with breast cancer, including noninvasive carcinoma, tended to increase in ascending order from LDH1 to LDH5. This pattern was similar to that in breast cancer tissue and was unrelated to the pattern in serum. CONCLUSION: LDH isozyme assay of nipple discharge may be a useful technique for providing a supporting diagnosis of breast cancer.