Pelosi G, Bresaola E, Bogina G, Pasini F, Rodella S, Castelli S, Iacono C, Serio G, Zamboni GEndocrine tumors of the pancreas: Ki-67 immunoreactivity on paraffin sections is an independent predictor for malignancy. A comparative study with PCNA and progesterone receptor protein immunostaining, mitotic index, and other clinicopathologic variables. Hum Pathol 27: 1124-1134
Prediction for malignancy of pancreatic endocrine tumors (PET) is often a formidable challenge for the pathologist. The authors evaluated the role of the proliferative activity and progesterone receptor protein (PgRP) in predicting prognosis and survival of PET. Twenty-three functioning (FT) and 31 nonfunctioning tumors (NFT) were evaluated for mitotic activity and immunostaining for Ki-67 antigen, proliferating cell nuclear antigen (PCNA), and progesterone receptor protein (PgRP) on paraffin sections. The results were expressed as a percentage (index) of immunoreactive or mitosing cells. All 54 cases showed immunostaining for Ki-67 and PCNA, and valuable mitotic index, whereas only a fraction of tumors (25 of 54 cases) exhibited PgRP expression. Ki-67 and PCNA indexes correlated strongly between themselves and to mitotic index, whereas an inverse relationship was observed between cell proliferation and PgRP status in both FT and NFT. Although univariate analysis showed that Ki-67, PCNA, mitotic and PgRP indexes, stage, immunoreactivity for hormones other than insulin, diameter, and nonfunctioning type of tumor were statistically correlated to survival, Cox's regression method let only Ki-67 index emerge as an independent predictor of survival using a cutoff value of 5% in both FT and NFT.
"A World Health Organization (WHO) classification system  is used to divide tumors into three groups: well-differentiated neuroendocrine tumors, well-differentiated neuroendocrine carcinomas, and poorly differentiated neuroendocrine carcinomas. Ki-67 has been demonstrated to have prognostic value using a cutoff of 2, 5, or 10% [1, 4, 6–10]. "
[Show abstract][Hide abstract] ABSTRACT: Better prognostic markers are needed for pancreatic endocrine tumors. Survivin is an apoptosis inhibitor that is suggested to have a negative prognostic impact in several tumor types. Contradictory data exist, especially regarding the significance of a nuclear versus cytoplasmic location of survivin. The prognostic relevance of nuclear and cytoplasmic survivin expression in pancreatic endocrine tumors-controlled for the tumor Ki-67 index, World Health Organization classification, and TNM stage-was investigated.
A total of 111 patients treated at a tertiary referral center were retrospectively evaluated. Clinical data were gathered from medical records. Immunohistochemistry for survivin and Ki-67 was performed on paraffin-embedded tissue. Univariate and multivariate Cox analyses were performed.
Patients with tumors that had <5% survivin-positive nuclei had a mean survival of 225 months [95% confidence interval (CI) 168-281]. The corresponding figure for patients with 5 to 50% survivin-positive tumor cell nuclei was 101 months [95% CI 61-140; hazard ratio (HR) 2.4; P < 0.01) and with >50% survivin-positive nuclei 47 months (95% CI 24-71; HR 4.9; P < 0.001). Nuclear survivin expression in >50% of the tumor cells was an independent marker of a poor prognosis (HR 5.7; P < 0.01). Cytoplasmic survivin was not a significant prognostic factor in the multivariate analysis (HR 0.94; P = 0.90).
High expression of nuclear survivin is a significant marker of a poor prognosis in patients with a pancreatic endocrine tumor.
World Journal of Surgery 11/2011; 36(6):1411-8. DOI:10.1007/s00268-011-1345-7 · 2.64 Impact Factor
"Ki67 is a proliferation marker, expressed during the active phases of the cell cycle and absent from resting cells (Scholzen and Gerdes, 2000). The Ki67 index has often been correlated with clinical outcome in human INS (Pelosi et al., 1996; La Rosa et al., 2007, 2009). Our study indicated that high Ki67 expression results in a poor prognosis in canine INS. "
[Show abstract][Hide abstract] ABSTRACT: The establishment of reliable prognostic biomarkers for canine insulinoma are warranted to facilitate optimal patient management. Using univariate and multivariate analyses, the present study evaluated the prognostic power of several clinical and histopathological criteria, as well as the Ki67 index, in 26 dogs with insulinoma. On univariate analysis, stromal fibrosis within these tumours was found to be significantly predictive for survival, while tumour size, the Ki67 index, and TNM (Tumour, Node, Metastasis) stage were significant in the prognosis of both disease-free interval and survival time. On multivariate analysis, tumour size retained predictive power for disease-free intervals, while the Ki67 index proved prognostically significant for both the disease-free interval and overall survival time. This study demonstrates that, in addition to known factors such as tumour size and stage, Ki67 can act as a biomarker of insulinoma that can be used to predict clinical outcome.
The Veterinary Journal 07/2010; 185(1):62-7. DOI:10.1016/j.tvjl.2010.04.015 · 1.76 Impact Factor
"However, there are several caveats to consider in the interpretation of the results from these studies. First, most of these studies have reviewed a single-institution experience with PETs or CTs that have been surgically resected (Pelosi et al. 1992, La Rosa et al. 1996, Clarke et al. 1997, Hochwald et al. 2002, Jorda et al. 2003). Secondly, patients were considered to have advanced disease if they presented with either locoregional lymph node or distant metastasis (La Rosa et al. 1996, Clarke et al. 1997, Hochwald et al. 2002, Jorda et al. 2003). "
[Show abstract][Hide abstract] ABSTRACT: Neuroendocrine tumors (NETs) of the digestive tract are a heterogeneous group of rare malignancies. Three major subgroups can be defined: pancreatic endocrine tumors, carcinoid tumors, and poorly differentiated gastroenteropancreatic NETs. Classically, digestive NETS have been considered to have an indolent course characterized for prolonged stabilizations or slow progressions, but there are clear differences in terms of aggressiveness, clinical course, and response to treatment among them. Retrospective studies have identified several clinicopathological and immunohistochemical factors as angioinvasion and proliferative index assessed by Ki-67 expression, which predict biological behavior and correlate with survival. Chemotherapy regimens based on the combination of several active drugs such as streptozocin, doxorubicin, 5-fluorouracil, dacarbazine, and temozolomide show low response rates, which sets the need to improve the results of the medical treatment of these malignancies. This review will analyze the role of Ki-67 in digestive NETs under a clinical perspective and will suggest future fields for development of this approach that enable a better patient selection for chemotherapy. Also a comprehensive review of the literature about chemotherapy in NETs is presented.
Endocrine Related Cancer 07/2007; 14(2). DOI:10.1677/ERC-06-0074 · 4.81 Impact Factor
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