A Clinicopathologic Study on the Role of Estrogen, Progesterone, and Their Classical and Nonclassical Receptors in Cutaneous Neurofibromas of Individuals With Neurofibromatosis 1

2020 ◽  
Author(s):  
Rafaela E Rozza-de-Menezes ◽  
Lilian M Almeida ◽  
Raquel M Andrade-Losso ◽  
Gustavo de Souza Vieira ◽  
Orlando H K Siqueira ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Laboratory Data ◽  
Serum Levels ◽  
Neurofibromatosis 1 ◽  
Proliferation Index ◽  
Computer Assisted ◽  
Ki 67 ◽  
Clinicopathologic Study ◽  
Cutaneous Neurofibromas

Abstract Objectives To evaluate the expression of progesterone receptor (PR), estrogen receptor (ER), and G protein–coupled estrogen receptor 1 (GPER-1) in cutaneous neurofibromas (cNFs) and their correlation with demographic, clinical, and laboratory data of individuals with neurofibromatosis 1 (NF1). The association of PROGINS polymorphism and PR expression in cNFs, as well as the serum steroidal hormones and the number of cNFs, was investigated. Methods The sample comprised 80 large and 80 small cNFs from 80 individuals with NF1. PR, ER, GPER-1, and Ki-67 expression were investigated by immunohistochemistry in tissue micro- and macroarrays and quantified using a digital computer-assisted method. The number of cNFs, the levels of serum 17β estradiol and progesterone, and the PROGINS polymorphism were identified. Results Twelve (8.5%) small cNFs were weakly positive for ER, 131 (92.3%) cNFs expressed PR, and all (100%) cNFs expressed GPER-1. Large cNFs showed a higher expression of PR (P < .0001) and GPER-1 (P = .019) and had a higher intensity of staining for these receptors (P < .0001). The cell proliferation index was positively correlated with PR (P = .001). Persons with more cNFs had higher serum levels of progesterone (P = .001). Conclusions These findings emphasize the role of estrogen and progesterone in cNF development and suggest that these hormones may act on cNF cells via a noncanonical pathway through GPER-1.

scholarly journals Ghost cell odontogenic carcinoma: Role of p53 as predictor of progression

2020 ◽  
Vol 10 (1) ◽  
pp. 1675-1678
Author(s):  
Pallavi Srivastava ◽  
Nidhi Anand ◽  
Nuzhat Husain
Keyword(s):  
Distant Metastases ◽  
Proliferation Index ◽  
Ghost Cell ◽  
Ki 67 ◽  
Local Recurrences ◽  
Odontogenic Carcinoma ◽  
Fibular Flap ◽  
Slow Growing

Ghost cell odontogenic carcinoma (GCOC) a rare malignant Odontogenic Carcinoma with an unpredictable behaviour presenting with local recurrences and distant metastases, to best of our knowledge about 38 cases have been reported in the past. This is an additional case of GCOC in a 25-year old female presented with a slow-growing mandibular swelling since 9 months with restricted jaw mobility. The CT scan showed an ill-defined osteodestructive lesion in the mandible. The histological examination confirms the diagnoses as a GCOC. Immunohistochemical examination was performed for Ki-67 proliferation index and p53 a predictor of progression. This case was managed by wide surgical resection of tumor and reconstruction of the defect by free fibular flap. Six months follow- up period shows no signs of recurrence. GCOC is rare Odontogenic Carcinoma with unpredictable behaviour however p53 & Ki67 proliferation index can predict the progression of tumor and help in differentiation from benign precursor lesions as early diagnosis & treatment of GCOC is necessary to prevent local recurrences & distant metastases.

scholarly journals Adjuvant Therapy in Adrenocortical Carcinoma: Reflections and Future Directions

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 508 ◽  
Author(s):  
Sara Bedrose ◽  
Marilyne Daher ◽  
Lina Altameemi ◽  
Mouhammed Amir Habra
Keyword(s):  
Adjuvant Therapy ◽  
Surgical Resection ◽  
Adrenocortical Carcinoma ◽  
Genetic Alterations ◽  
Disease Stage ◽  
Proliferation Index ◽  
Resection Margins ◽  
Ki 67 ◽  
Platinum Based Chemotherapy

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with high risk of recurrence despite macroscopically complete surgical resection. The main predictors of ACC recurrence include advanced disease stage, incomplete surgical resection, cortisol production, certain genetic alterations, and high proliferation rate (Ki-67 proliferation index). Mitotane has been the mainstay adjuvant therapy of ACC. However, the use of mitotane is based on retrospective and occasionally conflicting evidence. As mitotane levels can take a few months before reaching therapeutic levels, there is an emerging practice of combining platinum-based chemotherapy with mitotane in the adjuvant setting. Retrospective data indicate that radiotherapy is an option for select patients, particularly those with positive resection margins. There are multiple knowledge gaps in selecting patients for adjuvant therapy. It is of great importance to establish risk calculators to predict recurrence and to implement molecular profiling of ACC to guide adjuvant therapy. The role of immunotherapy in metastatic ACC is emerging and if deemed efficacious, then future studies will be needed to ascertain the role of adjuvant immunotherapy in ACC.

Predictors of invasive breast cancer or DCIS recurrence in estrogen receptor positive (ER+) and estrogen receptor negative (ER-) ductal carcinoma in situ (DCIS) patients with and without associated invasive carcinoma (IC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11523-e11523 ◽  
Author(s):  
J. Picarsic ◽  
A. Brufsky ◽  
A. Onisko ◽  
M. Chivukula
Keyword(s):  
Estrogen Receptor ◽  
Biological Markers ◽  
Hormone Receptors ◽  
Invasive Carcinoma ◽  
Ductal Carcinoma ◽  
Response To Therapy ◽  
Proliferation Index ◽  
Low Grade ◽  
Ki 67 ◽  
Mib 1

e11523 Background: DCIS is a heterogeneous pre-invasive carcinoma with a spectrum of clinical behavior. Patients with ER+ IC have better outcomes compared to ER- patients. FOXA1 and GATA 3 family of transcription factors have been shown to be associated with hormone receptors (ER and PR) and other variables of good prognosis with better overall and relapse-free survival rate. The specific aim of this study is to analyze the expression of these novel biological markers: FOXA1, GATA-3, with recognized markers: MIB-1(Ki-67) and HER2 /neu in DCIS patients with/without associated IC. Methods: Sixty-nine (69) cases of DCIS [(fifty two (52) cases in ER+; seventeen (17) in ER-] were retrieved from our Pathology database. The expressions of the biological markers are analyzed by using a panel of immunohistochemical stains. FOXA1, GATA 3, ER, PR are nuclear stains, a cumulative “H score” is derived based on proportionality (PS) and intensity scores (IS). A proliferation index (PI) is calculated for MIB-1 (Ki67) nuclear stain (low <10%, moderate 11–25%, high 26–50%, very high>50%). Her2/neu is scored as per guidelines for HercepTest (0, or 1+ =negative, 2+ =weakly positive, 3+ =strongly positive). Results: DCIS is categorized into low grade (LG) (nuclear grade 1 and 2), high grade (HG) (grade 3). In the HGDCIS (n=48), four (4) cases had IC after a mean of 7.75 years; three cases of recurrent DCIS after a mean 6 years. No recurrent IC or DCIS is seen in the LGDCIS (n=21) group. The results are shown in the Table . Conclusions: (1) Decreased expression of GATA 3 is observed in HGDCIS ER- group may be a contributor to higher recurrence observed in this group (14%) versus (0%) in ER+ group. (2) A strong expression of FOXA, GATA3, low Ki-67 index, absent Her 2 expression are characteristically seen in our ER+ DCIS group, as previously described in IC. 3. Comparing the response to therapy and outcome in the ER+ and ER- groups is on going. [Table: see text] No significant financial relationships to disclose.

The role of Ki-67 proliferation index vis-à-vis Oncotype DX.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. e11055-e11055
Author(s):  
S. Sahebjam ◽  
R. Aloyz ◽  
D. Pilavdzic ◽  
M. Brisson ◽  
C. Ferrario ◽  
...  
Keyword(s):  
Oncotype Dx ◽  
Proliferation Index ◽  
Ki 67

Role of cyclins D1 and D3 in vestibular schwannoma

2015 ◽  
Vol 130 (S1) ◽  
pp. S2-S10 ◽  
Author(s):  
J Jabbour ◽  
P Earls ◽  
N Biggs ◽  
G Gracie ◽  
P Fagan ◽  
...  
Keyword(s):  
Vestibular Schwannoma ◽  
Age Groups ◽  
Vestibular Schwannomas ◽  
Proliferation Index ◽  
Cyclin D ◽  
Age Group ◽  
Ki 67 ◽  
Younger Age ◽  
Two Age Groups

AbstractBackground:Vestibular schwannomas in younger patients have been observed to be larger in size and grow more quickly.Objective:This study aimed to evaluate the expression of three important cell cycle proteins, cyclin D1, cyclin D3and Ki-67, in vestibular schwannoma patients separated into two age groups: ≤40 years or >40 years.Method:Immunohistochemical detection of cyclin D1, cyclin D3and Ki-67 was undertaken in 180 surgically resected vestibular schwannomas.Results:The proliferation index of vestibular schwannomas was statistically higher in the ≤40 years age group compared to that in the >40 years age group (mean of 4.52vs3.27, respectively;p = 0.01). Overexpression of cyclin D1and cyclin D3was found in 68 per cent and 44 per cent of tumours, respectively.Conclusion:There was an increased Ki-67 proliferation index in the younger age group that appears to correlate with clinical behaviour. Vestibular schwannomas in both age groups show increased expression of cyclin D1and cyclin D3.

Role of Ki-67 proliferation index and p53 expression in predicting progression of pituitary adenomas

2008 ◽  
Vol 39 (5) ◽  
pp. 758-766 ◽  
Author(s):  
Roger Gejman ◽  
Brooke Swearingen ◽  
E. Tessa Hedley-Whyte
Keyword(s):  
Pituitary Adenomas ◽  
Proliferation Index ◽  
Ki 67 ◽  
P53 Expression

scholarly journals Diagnostic and Interventional Role of Endoscopic Ultrasonography for the Management of Pancreatic Neuroendocrine Neoplasms

2021 ◽  
Vol 10 (12) ◽  
pp. 2638
Author(s):  
Giuseppinella Melita ◽  
Socrate Pallio ◽  
Andrea Tortora ◽  
Stefano Francesco Crinò ◽  
Antonio Macrì ◽  
...  
Keyword(s):  
Tumor Burden ◽  
Pancreatic Tumors ◽  
Proliferation Index ◽  
Neuroendocrine Neoplasms ◽  
Ki 67 ◽  
Ethanol Injection ◽  
Pancreatic Neuroendocrine Neoplasms ◽  
Reduce Tumor Burden ◽  
Precise Diagnosis

Pancreatic neuroendocrine neoplasms (PanNENs) are relatively rare, but their incidence has increased significantly in the last decades. Precise diagnosis and prognostic stratification are crucial for proper patient management. Endoscopic ultrasound (EUS) is the modality of choice for diagnosis of solid pancreatic tumors, showing a higher tumor detection rate than other imaging modalities, especially for small size lesions. EUS also serves as a guide for preoperative sampling and other interventions. EUS-tissue acquisition is a safe and highly accurate technique for cyto/histological diagnosis of PanNENs with a well-demonstrated correlation between Ki-67 proliferation index values and tumor grading on EUS and surgical specimens according to the WHO 2017 classification. Furthermore, the possibility of a preoperative EUS-guided fine needle tattooing or fiducial markers placement may help the surgeon to locate small and deep tumors, thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery. Finally, locoregional ablative treatments using either ethanol injection or radiofrequency ablation have been proposed in recent studies with promising results in order to control symptoms or reduce tumor burden in selected patients unfit for surgery with functioning or non-functioning PanNENs. This article review highlights the current role of EUS in PanNENs management, focusing on the present and future applications of EUS-guided interventions.

Mechanism of Villous Atrophy in Celiac Disease: Role of Apoptosis and Epithelial Regeneration

2013 ◽  
Vol 137 (9) ◽  
pp. 1262-1269 ◽  
Author(s):  
DM Shalimar ◽  
Prasenjit Das ◽  
Vishnubhatla Sreenivas ◽  
Siddhartha Datta Gupta ◽  
Subrat K. Panda ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Epithelial Cell ◽  
Villous Atrophy ◽  
Proliferation Index ◽  
Cell Regeneration ◽  
Ki 67 ◽  
Epithelial Regeneration ◽  
Treatment Naïve ◽  
Apoptotic Pathways

Context.—The data on status of apoptosis in patients with celiac disease are conflicting. Furthermore, complex interaction between intrinsic and common apoptotic pathways, apoptotic inhibitors, and epithelial cell proliferation is largely unclear for patients with celiac disease. Objectives.—To determine the role of apoptosis and epithelial cell regeneration in celiac disease. Design.—Twenty-five treatment-naïve patients with celiac disease and 6 patients with functional dyspepsia, as controls, were included and duodenal biopsy specimens from all were subjected to immunohistochemistry with markers of intrinsic apoptotic pathway (AIF, H2AX, p53), common pathway (CC3, M30), apoptotic inhibitors (XIAP, Bcl2), and epithelial proliferation (Ki-67). Apoptotic and proliferation indices were calculated. Results.—Expression of end-apoptotic products, that is, H2AX in the cell nuclei (P = .01) and M30 in the cell cytoplasm (P &lt; .01), was significantly upregulated in celiac disease in comparison to controls. Cleaved caspase-3 was also upregulated in villous cytoplasm in celiac disease. Apoptotic inhibitor Bcl2 was significantly down-regulated in celiac disease in comparison to controls. In addition, Ki-67 proliferation index was upregulated both in the crypts and villous mucosal epithelium in comparison to the crypts of the controls. Conclusions.—Treatment-naïve patients with celiac disease have significantly higher level of apoptosis that involves both the common and intrinsic apoptotic pathways. Increased apoptosis and unequaled cell regeneration in crypts probably results in villous atrophy. Down-regulation of apoptotic inhibitors in treatment-naïve celiac disease imparts an additional pro-apoptotic effect.

scholarly journals Mast Cells in Human Cutaneous Neurofibromas: Density, Subtypes, and Association with Clinical Features in Neurofibromatosis 1

Dermatology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Roope A. Kallionpää ◽  
Kaisa Ahramo ◽  
Eija Martikkala ◽  
Elnaz Fazeli ◽  
Pekka Haapaniemi ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Clinical Features ◽  
Disease Burden ◽  
Neurofibromatosis 1 ◽  
Computer Assisted ◽  
Unaffected Skin ◽  
Comprehensive Characterization ◽  
Cutaneous Neurofibromas

<b><i>Background:</i></b> Cutaneous neurofibromas (cNFs) are hallmarks of neurofibromatosis 1 (NF1) and cause the main disease burden in adults with NF1. Mast cells are a known component of cNFs. However, no comprehensive characterization of mast cells in cNFs is available, and their contributions to cNF growth and symptoms such as itch are not known. <b><i>Methods:</i></b> We collected 60 cNFs from ten individuals with NF1, studied their mast cell proteinase content, and compared the mast cell numbers to selected clinical features of the tumors and patients. The tumors were immunolabeled for the mast cell markers CD117, tryptase, and chymase, and the percentage of immunopositive cells was determined using computer-assisted methods. <b><i>Results:</i></b> The median proportions of positive cells were 5.5% (range 0.1–14.4) for CD117, 4.0% (1.2–7.0) for tryptase, and 5.0% (1.1–15.9) for chymase. The median densities of cells immunopositive for CD117, tryptase, and chymase were 280, 243, and 250 cells/mm<sup>2</sup>, respectively. Small tumors, growing tumors, and tumors from patients below the median age of 33 years displayed a high proportion of mast cells. Cells expressing both tryptase and chymase were the predominant mast cell type in cNFs, followed by cells expressing chymase only. <b><i>Conclusion:</i></b> The results highlight the abundance of mast cells in cNFs and that their number and subtypes clearly differ from those previously reported in unaffected skin.

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