scholarly journals Ki-67 Evaluation for Clinical Decision in Metastatic Lung Carcinoids: A Proof of Concept

2019 ◽  
Vol 12 ◽  
pp. 2632010X1982925 ◽  
Author(s):  
Giuseppe Pelosi ◽  
Federica Massa ◽  
Gaia Gatti ◽  
Luisella Righi ◽  
Marco Volante ◽  
...  
Keyword(s):  
Close Correlation ◽  
Clinical Decision ◽  
Somatostatin Analogues ◽  
Mitotic Count ◽  
Observer Agreement ◽  
Proof Of Concept ◽  
Metastatic Carcinoid ◽  
Ki 67 ◽  
Pulmonary Carcinoid ◽  
Platinum Based Chemotherapy

Accrual of metastatic pulmonary carcinoid patients for therapy is usually relied on clinical and histologic characterization, with no role for the proliferation activity as defined by Ki-67 labelling index (LI). A total of 14 carcinoid patients with tumour primaries (TP) and 19 corresponding tumour metastases (TM) were blindly reviewed by 2 different pathologists for necrosis, mitotic count, and Ki-67 LI. Ki-67 LI outperformed histologic subtyping, mitotic count, and necrosis with good to almost excellent (0.40-0.75) inter-observer agreement. About 10% cut-off Ki-67 LI predicted survival better than histology for TP and TM for both observers. The TM patients survived differently according to diverse treatments (somatostatin analogues [SSAs], analogues plus additional treatments except for platinum; platinum-based chemotherapy) in close correlation with <10%, 10% to 20%, and >20% cut-off thresholds of Ki-67 LI, respectively. There was also a trend for an increase in Ki-67 LI in TM as compared with TP. This is the first proof of concept in which a clinical potential is preliminarily suggested for Ki-67 LI to better stratify pulmonary metastatic carcinoid patients for treatment according to a criterion of histology-independent biological aggressiveness.

scholarly journals Neuroendocrine Carcinomas of the Digestive Tract: What Is New?

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3766
Author(s):  
Anna Pellat ◽  
Anne Ségolène Cottereau ◽  
Benoit Terris ◽  
Romain Coriat
Keyword(s):  
Peptide Receptor Radionuclide Therapy ◽  
Large Cell ◽  
Current Data ◽  
World Health ◽  
High Grade ◽  
Ki 67 ◽  
Lung Cancers ◽  
Platinum Based Chemotherapy ◽  
Line Setting ◽  
Neuroendocrine Carcinomas

Neuroendocrine carcinomas (NEC) are rare tumors with a rising incidence. They show poorly differentiated morphology with a high proliferation rate (Ki-67 index). They frequently arise in the lung (small and large-cell lung cancer) but rarely from the gastrointestinal tract. Due to their rarity, very little is known about digestive NEC and few studies have been conducted. Therefore, most of therapeutic recommendations are issued from work on small-cell lung cancers (SCLC). Recent improvement in pathology and imaging has allowed for better detection and classification of high-grade NEN. The 2019 World Health Organization (WHO) classification has described a new entity of well-differentiated grade 3 neuroendocrine tumors (NET G-3), with better prognosis, that should be managed separately from NEC. NEC are aggressive neoplasms often diagnosed at a metastatic state. In the localized setting, surgery can be performed in selected patients followed by adjuvant platinum-based chemotherapy. Concurrent chemoradiotherapy is also an option for NEC of the lung, rectum, and esophagus. In metastatic NEC, chemotherapy is administered with a classic combination of platinum salts and etoposide in the first-line setting. Peptide receptor radionuclide therapy (PRRT) has shown positive results in high-grade NEN populations and immunotherapy trials are still ongoing. Available therapies have improved the overall survival of NEC but there is still an urgent need for improvement. This narrative review sums up the current data on digestive NEC while exploring future directions for their management.

scholarly journals Poorly Differentiated Small-Cell-Type Neuroendocrine Carcinoma of the Prostate: A Case Report and Literature Review

2018 ◽  
Vol 11 (3) ◽  
pp. 676-681 ◽  
Author(s):  
Kishore Kumar ◽  
Rafeeq Ahmed ◽  
Chime Chukwunonso ◽  
Hassan Tariq ◽  
Masooma Niazi ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Tumor Grade ◽  
Small Cell ◽  
The Body ◽  
Neuroendocrine Cells ◽  
Cell Type ◽  
Variable Response ◽  
Ki 67 ◽  
Platinum Based Chemotherapy ◽  
Poorly Differentiated

Neuroendocrine cells are widespread throughout the body and can give rise of neuroendocrine tumors due to abnormal growth of the chromaffin cells. Neuroendocrine tumors divide into many subtypes based on tumor grade (Ki-67 index and mitotic count) and differentiation. These tumors can be further divided into secretory and nonsecretory types based on the production of peptide hormone by tumor cells. Poorly differentiated small-cell-type neuroendocrine tumors are one of the subtypes of neuroendocrine tumors. These tumors are less common; however, they tend to be locally invasive and aggressive in behavior with poor overall median survival. Treatment of the nonsecretory small-cell type is modeled to small-cell lung cancer with a regimen consisting of platinum-based chemotherapy and etoposide with variable response. Here, we present a case of poorly differentiated small-cell neuroendocrine tumor originating from the prostate.

Chemoprevention with Enalapril and Aspirin in Men1(+/T) Knockout Mouse Model

2018 ◽  
Vol 107 (3) ◽  
pp. 257-266 ◽  
Author(s):  
Jerena Manoharan ◽  
Volker Fendrich ◽  
Pietro Di Fazio ◽  
Carmen Bollmann ◽  
Silvia Roth ◽  
...  
Keyword(s):  
Mouse Model ◽  
Somatostatin Analogues ◽  
Control Group ◽  
Histopathological Analysis ◽  
Ki 67 ◽  
Chemopreventive Agents ◽  
Knockout Mouse Model ◽  
Angiotensin I Converting Enzyme ◽  
Significant Difference

Pancreatic neuroendocrine neoplasias (pNEN) are the most common cause of death in adult patients with multiple endocrine neoplasia type 1 (MEN1). So far, only few chemopreventive strategies (e.g., with somatostatin analogues) have been evaluated for MEN1 associated pNENs. In this experimental study on 75 Men1(+/T) knockout mice, the effect of aspirin (n = 25) and an inhibitor of angiotensin-I converting enzyme (enalapril, n = 25) compared to controls (n = 25) were evaluated as single chemopreventive strategies for pNENs after 6, 9, 12, 15, and 18 months. After each study period, mice were sacrificed and the resected pancreata were evaluated by histopathological analysis, immunostaining, and real-time PCR. PNEN size and number was measured. Aspirin and enalapril lead to a pNEN size reduction of 80% (167,518 vs. 838,876 µm2, p < 0.001) and 79% (174,758 vs. 838,876 µm2, p < 0.001) compared to controls. Furthermore, aspirin and enalapril treatment resulted in a significant reduction of the number of pNENs by 33%, (p = 0.04) and 41% (p = 0.002) respectively. The apoptosis marker caspase 3 revealed a higher positive expression in pNEN of treated Men1(+/T) mice. Immunostaining of VEGF in pNEN detected a downregulation of its expression in treated Men1(+/T) mice compared to the control group. REL A transcript was significantly downregulated in 18-months treated enalapril Men1(+/T) mice, but not in aspirin-treated Men1(+/T) mice. There was no significant difference in the Ki-67 index. Using a transgenic mouse model that imitates human MEN1, this study provides first evidence that aspirin and enalapril are effective chemopreventive agents that aid in the progression of pNENs.

scholarly journals Current Paradigm of Treatment for Pancreatic Neuroendocrine Tumor

2021 ◽  
Vol 26 (1) ◽  
pp. 24-32
Author(s):  
Min Je Sung ◽  
Moon Jae Chung
Keyword(s):  
Cell Proliferation ◽  
Medical Treatment ◽  
Neuroendocrine Tumor ◽  
Standard Treatment ◽  
Pancreatic Neuroendocrine Tumor ◽  
Somatostatin Analogues ◽  
Proliferation Index ◽  
Ki 67 ◽  
Grade 3 ◽  
Cell Proliferation Index

Pancreatic neuroendocrine tumor (PNET) refer to tumors originating from the islet of Langerhans and shows various prognosis based on the presence or absence of symptoms due to hormone secretion, the Ki-67 cell proliferation index, and the histologic grade, and according to the degree of disease progression defined by the tumor-node-metastasis (TNM) stage classification. The purpose of medical treatment for PNET is to control symptoms or inhibit tumor growth. Somatostatin analogues can be administered for the purpose of controlling symptoms caused by the secretion of specific hormones, and are accepted as effective drugs for inhibiting the progression of G1/G2 tumors based on World Health Organization (WHO) classification with a Ki-67 cell proliferation index less than 20%. Among the molecularly targeted agents, everolimus and sunitinib can be considered in patients with WHO G1/G2 PNET showing progression after somatostatin analog therapy. Cytotoxic chemotherapy is generally administered to patients with large tumor volume and rapidly progressing metastatic NET, and etoposide/cisplatin combination therapy has been considered as a standard treatment. For the patient group of Grade 3 PNET (well differentiated) newly classified by the WHO 2017 classification, guidelines for standard treatment have not yet been established. As it has been reported, studies are needed to evaluate the treatment response rate of somatostatin analogues or molecularly targeted therapies for the patient with Grade 3 PNET. It is important to consider a multidisciplinary approach with all possible treatment options including medical treatment, radical resection of primary or metastatic lesions, liver-directed therapies, and peptide receptor radionuclide therapy for the patients with PNET.

DNA Topoisomerase II-α and Cyclin A Immunoexpression in Meningiomas and Its Prognostic Significance

2002 ◽  
Vol 126 (9) ◽  
pp. 1079-1086
Author(s):  
Andrey Korshunov ◽  
Lyudmila Shishkina ◽  
Andrey Golanov
Keyword(s):  
Topoisomerase Ii ◽  
Tumor Grade ◽  
Cyclin A ◽  
Close Correlation ◽  
Hazard Ratio ◽  
Benign Tumors ◽  
Ki 67 ◽  
Dna Topoisomerase ◽  
Proliferative Markers ◽  
Topoisomerase Ii Α

Abstract Context.—Routine pathologic examination cannot distinctively predict the clinical course of meningiomas because even histologically benign tumors may recur after gross total resection. Therefore, numerous efforts have been made to evaluate the meningioma growth fraction and its prognostic value. However, a universally applicable proliferative marker for meningioma outcome is not yet a reality. Objective.—To investigate the prognostic utility of 3 proliferative markers, namely, Ki-67, DNA topoisomerase II-α (topoII), and cyclin A in a representative series of intracranial meningiomas. Design.—Two hundred sixty-three adult patients with intracranial meningiomas (208 benign, 42 atypical, and 13 anaplastic) were studied retrospectively. Tumor specimens were immunohistochemically examined with antibodies to Ki-67 (MM-1), topoII, and cyclin A. A computerized color image analyzer was used to count immunostained nuclei. Results.—The topoII and cyclin A scores exhibited a close correlation with Ki-67 immunostaining. Significant differences between the indices for all 3 markers were noted among the 3 grades of meningiomas. The scores for all 3 markers were significantly different between recurrent and nonrecurrent meningiomas, including benign tumors that were treated with gross total resection. Recurrence-free survival was significantly reduced for cases with a Ki-67 labeling index (LI) of 4.4% or greater, a topoII LI of 3.2% or greater, and a cyclin A LI of 3.1% or greater. Multivariate analysis revealed that the risk of recurrence for the entire meningioma cohort was significantly associated with tumor grade (hazard ratio = 2.7; P = .004), topoII LI of 3.2% or greater (hazard ratio = 5.5; P &lt; .001), and a cyclin A LI of 3.1% or greater (hazard ratio = 2.4; P = .01). Conclusions.—There is a close correlation in the expression of these 3 proliferative markers in meningiomas, and all of the markers showed a significant association with tumor grade, recurrence rate, and recurrence-free survival. Consequently, in addition to Ki-67, immunoexpression of topoII and cyclin A is available for predicting meningioma recurrence. Moreover, the topoII and cyclin A staining scores were found to be more sensitive predictors for meningioma progression than Ki-67 and, therefore, either of these 2 markers may prove to be clinically informative and useful.

Gastrointestinal Stromal Tumors: A “Benign” Tumor with Hepatic Metastasis after 11 Years

1998 ◽  
Vol 84 (1) ◽  
pp. 78-81 ◽  
Author(s):  
Carlo Ballarini ◽  
Mattia Intra ◽  
Andrea Pisani Ceretti ◽  
Francesco Prestipino ◽  
Filippo Maria Bianchi ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Hepatic Metastasis ◽  
Tumor Size ◽  
Gastrointestinal Stromal Tumors ◽  
Cellular Proliferation ◽  
Malignant Potential ◽  
Mitotic Count ◽  
Proliferation Index ◽  
Ki 67 ◽  
Stromal Tumors

Gastrointestinal stromal tumors (GIST) constitue the largest category of primary non-epithelial neoplasms of the stomach and small bowel. They are characterized by a remarkable cellular variability and their malignant potential is sometimes difficult to predict. Very recent studies, using mitotic count and tumor size as the best determinants of biological behavior, divide GISTs into three groups: benign, borderline and malignant tumors. We report on a male patient who underwent a right hepatectomy for a large metastasis 11 years after the surgical treatment of an antral-pyloric gastric neoplasm, histologically defined as leiomyoblastoma and with clinical, morphological and immunohistochemical features of benignity (low mitotic count, tumor size < 5 cm, low cellular proliferation index). Histological and immunohistochemical analysis of the hepatic metastasis showed the cellular proliferation index (Ki-67) to be positive in 25% of neoplastic cells, as opposed to the primary gastric tumor in which Ki-67 was positive in only 5% of neoplastic cells. In conclusion, although modern immunohistochemical techniques are now available to obtain useful prognostic information, the malignant potential of GISTs is sometimes difficult to predict: neoplasms clinically and histologically defined as benign could metastasize a long time after oncologically correct surgical treatment. Therefore, benign GISTs also require consistent, long-term follow-up.

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