Predictive value of morphological features and proliferative markers (mitotic index, Ki-67, PHH3) in bronchopulmonary neuroendocrine tumors

The aim of this study was to evaluate relations of mitotic index (MI), necrosis, IHC proliferative markers Ki-67 and PHH3, and their predictive value for lung neuroendocrine tumors (NETs) aggressiveness. Materials and methods. The study used surgical and biopsy material from 64 patients with lung NETs before chemotherapy prescribing. Morphological study and IHC was performed. MI, necrosis, Ki-67 and PHH3 expression and metastatic disease and survival were estimated using nonparametric statistics. Results. Statistically significant association of necrosis severity and survival rates was found (P = 0.021). This was true for comparing patients with no necrosis in tumor tissue and extensive foci of necrosis (P = 0.023). MI appeared to be associated with metastases in lymph nodes (P = 0.003) and with distant metastatic lesions (P = 0.029). Significant, direct association of Ki-67 and MI (P < 0.001), MI and PHH3 expression (P < 0.001) was found. However, there was no significant link between Ki-67 and PHH3 rates (P = 0.240). Ki-67 didn’t show any significant association with necrosis and metastases. Also, Ki-67 rates didn’t affect the patient survival. Data on PHH3 expression and their estimation appeared to be rather contradictory. PHH3 expression rates were lower than expected and did not exceed neither Ki-67 rates, nor MI. Conclusions. MI and necrosis are reliable markers for the assessment of lung NETs aggressiveness. MI is statistically associated with metastatic lesion, while extensive necrosis – with survival rates. Ki-67 expression was significantly associated with MI. No significant association of Ki-67 and PHH3 expression, tumor’s morphological features, disease progression and prognosis was found. Contrary to our expectations, PHH3 showed no diagnostic and prognostic value in lung NETs.

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Are Cystic Pancreatic Neuroendocrine Tumors an Indolent Entity Results from a Single-Center Surgical Series

Neuroendocrinology ◽

10.1159/000477849 ◽

2017 ◽

Vol 106 (3) ◽

pp. 234-241 ◽

Cited By ~ 10

Author(s):

Salvatore Paiella ◽

Giovanni Marchegiani ◽

Marco Miotto ◽

Anna Malpaga ◽

Harmony Impellizzeri ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Survival Rates ◽

Disease Free Survival ◽

Postoperative Outcome ◽

Tumor Diameter ◽

Pancreatic Neuroendocrine Tumors ◽

Ki 67 ◽

Excellent Outcome ◽

Comparison Results ◽

Well Differentiated

Introduction: Cystic pancreatic neuroendocrine tumors (CPanNETs) represent an uncommon variant of pancreatic neuroendocrine tumors (PanNETs). Due to their rarity, there is a lack of knowledge with regard to clinical features and postoperative outcome. Methods: The prospectively maintained surgical database of a high-volume institution was queried, and 46 resected CPanNETs were detected from 1988 to 2015. Clinical, demographic, and pathological features and survival outcomes of CPanNETs were described and matched with a population of 92 solid PanNETs (SPanNETs) for comparison. Results: CPanNETs accounted for 7.8% of the overall number of resected PanNETs (46/587). CPanNETs were mostly sporadic (n = 42, 91%) and nonfunctioning (39%). Two functioning CPanNETs were detected (4.3%), and they were 2 gastrinomas. The median tumor diameter was 30 mm (range 10-120). All tumors were well differentiated, with 38 (82.6%) G1 and 8 (17.4%) G2 tumors. Overall, no CPanNET showed a Ki-67 >5%. A correct preoperative diagnosis of a CPanNET was made in half of the cases. After a median follow-up of >70 months, the 5- and 10-year overall survival of resected CPanNETs was 93.8 and 62.5%, respectively, compared to 92.7 and 84.6% for SPanNETs (p > 0.05). The 5- and 10-year disease-free survival rates were 94.5 and 88.2% for CPanNETs and 81.8 and 78.9% for SPanNETs, respectively (p > 0.05). Conclusion: In the setting of a surgical cohort, CPanNETs are rare, nonfunctional, and well-differentiated neoplasms. After surgical resection, they share the excellent outcome of their well-differentiated solid counterparts for both survival and recurrence.

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PROGNOSTIC ROLE OF KI - 67 INDEX AND MITOTIC INDEX IN NEUROENDOCRINE TUMORS OF HETEROGENOUS ORIGIN

Journal of Evolution of Medical and Dental Sciences ◽

10.14260/jemds/2014/3937 ◽

2014 ◽

Vol 3 (67) ◽

pp. 14438-14444

Author(s):

Triveni B ◽

Sandeep Kumar ◽

Sai Mallikarjun S ◽

Lakshmi Sri

Keyword(s):

Mitotic Index ◽

Neuroendocrine Tumors ◽

Prognostic Role ◽

Ki 67

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How to Classify Pituitary Neuroendocrine Tumors (PitNET)s in 2020

Cancers ◽

10.3390/cancers12020514 ◽

2020 ◽

Vol 12 (2) ◽

pp. 514 ◽

Cited By ~ 10

Author(s):

Jacqueline Trouillas ◽

Marie-Lise Jaffrain-Rea ◽

Alexandre Vasiljevic ◽

Gérald Raverot ◽

Federico Roncaroli ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Early Recognition ◽

Pituitary Tumors ◽

Operative Management ◽

Prognostic Impact ◽

Null Cell ◽

Ki 67 ◽

Standardized Report ◽

Proliferative Markers ◽

Morphologic Type

Adenohypophyseal tumors, which were recently renamed pituitary neuroendocrine tumors (PitNET), are mostly benign, but may present various behaviors: invasive, “aggressive” and malignant with metastases. They are classified into seven morphofunctional types and three lineages: lactotroph, somatotroph and thyrotroph (PIT1 lineage), corticotroph (TPIT lineage) or gonadotroph (SF1 lineage), null cell or immunonegative tumor and plurihormonal tumors. The WHO 2017 classification suggested that subtypes, such as male lactotroph, silent corticotroph and Crooke cell, sparsely granulated somatotroph, and silent plurihormonal PIT1 positive tumors, should be considered as “high risk” tumors. However, the prognostic impact of these subtypes and of each morphologic type remains controversial. In contrast, the French five-tiered classification, taking into account the invasion, the immuno-histochemical (IHC) type, and the proliferative markers (Ki-67 index, mitotic count, p53 positivity), has a prognostic value validated by statistical analysis in 4 independent cohorts. A standardized report for the diagnosis of pituitary tumors, integrating all these parameters, has been proposed by the European Pituitary Pathology Group (EPPG). In 2020, the pituitary pathologist must be considered as a member of the multidisciplinary pituitary team. The pathological diagnosis may help the clinician to adapt the post-operative management, including appropriate follow-up and early recognition and treatment of potentially aggressive forms.

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Predictive Value of Tumor Proliferative Indices in Periampullary Cancers: Ki-67, Mitotic Activity Index (MI) and Volume Corrected Mitotic Index (M/V) Using Tissue Microarrays

World Journal of Surgery ◽

10.1007/s00268-010-0681-3 ◽

2010 ◽

Vol 34 (9) ◽

pp. 2115-2121 ◽

Cited By ~ 6

Author(s):

Mark M. Aloysius ◽

Shivanthi J. De Silva Hewavisenthi ◽

Timothy E. Bates ◽

Brian J. Rowlands ◽

Dileep N. Lobo ◽

...

Keyword(s):

Mitotic Activity ◽

Mitotic Index ◽

Predictive Value ◽

Activity Index ◽

Tissue Microarrays ◽

Ki 67 ◽

Mitotic Activity Index ◽

Proliferative Indices

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P-111 Correlation of Mitotic Index and Ki-67 and Their Impacts on Survival of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) at Ramathibodi Hospital

Annals of Oncology ◽

10.1093/annonc/mdw199.105 ◽

2016 ◽

Vol 27 ◽

pp. ii33

Author(s):

T. Dejthevaporn ◽

V. Jennetisin ◽

S. Rattanasiri ◽

P. Sornmayura

Keyword(s):

Mitotic Index ◽

Neuroendocrine Tumors ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Ki 67

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Dual-color immunocytochemistry (Ki-67 with LCA) for precise grading of pancreatic neuroendocrine tumors with applicability to small biopsies and cell blocks

CytoJournal ◽

10.25259/cytojournal_92_2019 ◽

2020 ◽

Vol 17 ◽

pp. 6 ◽

Cited By ~ 1

Author(s):

Linette Mejías-Badillo ◽

Joshua Jeanty ◽

Kashan Khalid ◽

Amarpreet Bhalla ◽

Nagla Salem ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Fine Needle Aspiration ◽

Stromal Cells ◽

Pilot Project ◽

Needle Aspiration ◽

Cell Nuclei ◽

Biopsy Material ◽

Ki 67 ◽

Fine Needle ◽

Dual Color

Ki-67 (MIB-1) immunostaining to quantify the proliferative index of neuroendocrine tumors (NETs) has been recommended (especially for small biopsies). However, this has a number of challenges with nonrepresentative Ki-67 index due to interference by Ki-67 immunoreactive proliferating lymphocytes infiltrating the tumor and also some proliferating stromal cells including endothelial cells in the background. Our pilot project showed that dual-color immunostaining with inclusion of leukocyte common antigen (LCA) (Ki-67: nuclear brown; LCA: cytoplasmic red) can facilitate the weeding out of lymphocyte interference. We analyzed the results with 23 surgical cases of pancreatic NETs. This was followed by poststudy examination of 11 cases of endoscopic ultrasound-guided fine-needle aspiration of the pancreatic NETs (PanNETs) to evaluate the findings of the study. Dual-color immunostaining for Ki-67 with LCA increased the precision of quantifying Ki-67 index, due to ability to exclude LCA immunoreactive lymphocytes. Other nontumor Ki-67 immunoreactive cells such as endothelial and stromal cells could be distinguished morphologically. Digital methods were also attempted, but this approach could not distinguish infiltrating lymphocytes and other cells in sections resulting in erroneous results. This study demonstrated that grading of PanNET can be performed with increased precision with dual-color Ki-67 immunostaining protocol standardized in this study. As evaluated on a few cytopathology cases, this protocol is especially useful for the evaluation of small biopsies and cell block sections of fine-needle aspiration biopsy material where 50 high-power fields cannot be evaluated but have >500 tumor cell nuclei.

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Management and Prognostic Prediction of appendiceal mucinous adenocarcinoma with peritoneal metastasis: a single center study in China

10.21203/rs.2.17485/v1 ◽

2019 ◽

Author(s):

Ruiqing Ma ◽

Bing Wang ◽

Xichao Zhai ◽

Yiyan Lu ◽

Hongbin Xu

Keyword(s):

Survival Data ◽

Peritoneal Metastasis ◽

Mucinous Adenocarcinoma ◽

Proportional Hazards ◽

Survival Rates ◽

Cox Proportional Hazards ◽

Rank Test ◽

Ki 67 ◽

Kaplan Meier ◽

Prognostic Prediction

Abstract Background To investigate the clinical and pathological characteristics of appendiceal mucinous adenocarcinoma with peritoneal metastasis and analyze the prognostic factors.Methods A retrospective analyses of clinicopathological features of 50 patients with appendiceal mucinous adenocarcinoma with peritoneal metastasis from January, 2013 to December, 2017 in Aerospace Central Hospital, Beijing, China. Survival data calculation and comparison were respectively performed with the Kaplan-Meier method and the log-rank test. The Cox proportional hazards regression method was used for multivariate survival analyses.Results Cytoreduction for appendiceal mucinous adenocarcinoma was conducted on 50 patients (24 males and 26 females), with a median age of 52.5 years at the time of surgery (range 31-71 years). The median overall survival (OS) time was 24 months, with 2-,3- and 5-year survival rates of 53%, 24% and 8%, respectively. At the last follow-up in December 2018, 13 patients were still alive. Multivariate analysis revealed that patients who had low Ki-67 expression (less than 50%) and CCR (completeness of cytoreduction) 0/1/2 score had significantly better OS rate than their respective counterparts.Conclusions Ki-67 expression statue and CCR score could be employed as the prognosis prediction in patients with appendiceal mucinous adenocarcinoma.

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Immunohistochemical expression of markers Ki-67, neun, synaptophysin, p53 and HER2 in medulloblastoma and its correlation with clinicopathological parameters

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2008000300020 ◽

2008 ◽

Vol 66 (2b) ◽

pp. 385-390 ◽

Cited By ~ 14

Author(s):

Rosalva Thereza Meurer ◽

Daniele Tondolo Martins ◽

Arlete Hilbig ◽

Marlise de Castro Ribeiro ◽

Adriana Vial Roehe ◽

...

Keyword(s):

Brain Tumor ◽

Neuronal Differentiation ◽

Mitotic Index ◽

Survival Rates ◽

Clinicopathological Parameters ◽

Statistical Association ◽

Immunohistochemical Expression ◽

Ki 67 ◽

Clinicopathologic Parameters ◽

Tumor In Childhood

Medulloblastoma (MB) is the most common malignant brain tumor in childhood. The alterations found include: presence of oncoproteins p53 and HER2, elevated mitotic index, and presence of neuronal differentiation. The aim of this study was to determine the immunohistochemical expression of markers Ki-67, NeuN, synaptophysin, HER2 and p53 in 40 MB samples and their correlation with clinicopathologic parameters and survival. In 29 patients (72.5%), >20% of cells were positive for Ki-67. Males showed greater ki-67 expression (p=0.02) and smaller survival rates (p=0.002). NeuN and synaptophysin were negative in 16 (40%) and 8 (20%) cases, respectively. P53 was positive in 18 (45%) cases, with 11 (61%) weakly positive and 7 (39%) strongly positive. HER2 was positive in 23 (57.5%) of the samples and did not show statistical association with survival (p=0.07).

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Typical and Atypical Carcinoid Tumors of the Mediastinum: A Biomarker Analysis of 27 Cases With Clinical Correlation

International Journal of Surgical Pathology ◽

10.1177/1066896920976845 ◽

2020 ◽

pp. 106689692097684

Author(s):

Michael Zaleski ◽

Neda Kalhor ◽

Cesar A. Moran

Keyword(s):

Clinical Outcome ◽

Survival Data ◽

Tumor Size ◽

Survival Rates ◽

Carcinoid Tumors ◽

Clinical Correlation ◽

Atypical Carcinoid ◽

Ki 67 ◽

Biomarker Analysis ◽

Prognostic Utility

Thymic typical and atypical carcinoids are rare and appear to be more aggressive than similar tumors in other sites. We retrospectively analyzed a group of biomarkers that hold therapeutic and prognostic utility, in 27 of these tumors. All cases were immunohistochemically stained with PAX5, MET, CRMP5, paxillin, p21, p27, EZH2, PDL-1, and Ki-67, and then H-scored. Clinicopathologic and survival data were statistically analyzed against staining (χ2 test). Five- and 10-year-survival rates were 53% and 18%, respectively. Mitotic counts ≥4 per 2 mm2 and tumor size ≥5 cm, associated with death of disease (DoD; P = .010 and .016). Ki-67 expression ≥1% associated with DoD ( P = .003) and death within 5 years ( P = .031). Biomarkers stained tumor cases as follows: PDL-1 = 0%, PAX-5 = 0%, MET = 7.4%, paxillin = 41%, CRMP5 = 78%, p21 = 63%, p27 = 63%, EZH2 = 37%, and MASH1 = 59%. Overall ± staining did not associate with survival or grade. Cases with low CRMP5 H-scores (<80) associated with DoD ( P = .002), while CRMP5 H-scores >80 associated with 10-year survival ( P = .022). Cases with high MASH1 H-score (>100) associated with DoD ( P = .021). Accurate grading and staging remain paramount in predicting clinical outcome. Biomarkers may have significance in subsets of patients and the use of these studies likely should be focused on a more personalize type of approach.

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