Analysis of proliferation markers and p53 expression in gliomas of astrocytic origin: relationships and prognostic value

1997 ◽  
Vol 86 (1) ◽  
pp. 121-130 ◽  
Author(s):  
Julie M. Cunningham ◽  
David W. Kimmel ◽  
Bernd W. Scheithauer ◽  
Judith R. O'Fallon ◽  
Paul J. Novotny
Keyword(s):  
Univariate Analysis ◽  
Tumor Grade ◽  
Nuclear Antigen ◽  
Clinicopathological Parameters ◽  
Proliferative Potential ◽  
Ki 67 ◽  
Proliferation Markers ◽  
P53 Expression ◽  
Content Type ◽  
Mib 1

✓ Consecutive paraffin sections of 105 astrocytomas and 15 oligoastrocytomas were examined for expression of p53, MIB-1 (Ki-67), and proliferating cell nuclear antigen (PCNA). The tumors had been examined previously for genetic abnormalities and by flow cytometry. Regardless of the tumor's stage and grade and the patient's age and gender, p53 expression was found in 40% of tumors. Although p53 expression was associated with a loss on chromosome 17p and was more frequent in aneuploid tumors, it had no association with survival time. The MIB-1 and PCNA labeling indices increased with increasing tumor grade but showed no association with other clinicopathological parameters. In individual tumors, there was poor concordance between any of the variables (MIB-1, PCNA, and p53). Results for p53 and MIB-1 were similar for both astrocytomas and oligoastrocytomas. The MIB-1 and PCNA values appeared to have prognostic utility in univariate analysis but not after adjusting for patient age and tumor grade. The poor concordance between MIB-1 and PCNA in individual tumors indicates that any one means of assessing proliferative potential in gliomas may not be reliable.

scholarly journals Changes in Cellular Regulatory Factors before and after Decompression of Odontogenic Keratocysts

2020 ◽  
Vol 10 (1) ◽  
pp. 30
Author(s):  
Slmaro Park ◽  
Han-Sung Jung ◽  
Young-Soo Jung ◽  
Woong Nam ◽  
Jung Yul Cha ◽  
...  
Keyword(s):  
Recurrence Rate ◽  
Biological Behavior ◽  
Nuclear Antigen ◽  
Epithelial Cyst ◽  
Ki 67 ◽  
Proliferation Markers ◽  
Odontogenic Keratocysts ◽  
Wide Range ◽  
Before And After ◽  
Cyst Lining

Decompression followed by enucleation, which is one of the treatments used for odontogenic keratocysts (OKCs), is frequently used in OKC lesions of large sizes. This method offers the advantage of minimizing the possibility of sensory impairment without creating a wide-range bone defect; moreover, the recurrence rate can be significantly lower than following simple enucleation. This study aimed to assess the changes in histology and expression of proliferation markers in OKCs before and after decompression treatment. A total of 38 OKC tissue samples from 19 patients who had undergone decompression therapy were examined morphologically and immunohistochemically to observe changes in proliferative activity before and after decompression. The markers used for immunohistochemistry (IHC) staining were Bcl-2, epidermal growth factor receptor (EGFR), Ki-67, P53, PCNA, and SMO. The immunohistochemistry positivity of the 6 markers was scored by using software ImageJ, version 1.49, by quantifying the intensity and internal density of IHC-stained epithelium. The values of Bcl-2, Ki-67, P53, proliferating cell nuclear antigen (PCNA), and SMO in OKCs before and after decompression showed no significant change. No correlation between clinical shrinkage and morphologic changes or expression of proliferation and growth markers could be found. There was no statistical evidence that decompression treatment reduces potentially aggressive behavior of OKC within the epithelial cyst lining itself. This might indicate that decompression does not change the biological behavior of the epithelial cyst lining or the recurrence rate.

scholarly journals Immunohistochemical WWOX Expression and Association with Angiogenesis, p53 Expression, Cell Proliferation and Clinicopathological Parameters in Cervical Cancer

2018 ◽  
Vol 40 (02) ◽  
pp. 079-085 ◽  
Author(s):  
Mariana Seabra ◽  
Eduardo Cândido ◽  
Paula Vidigal ◽  
Rivia Lamaita ◽  
Angélica Rodrigues ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cervical Squamous Cell Carcinoma ◽  
Pelvic Lymphadenectomy ◽  
Histological Evaluation ◽  
Clinicopathological Parameters ◽  
Control Group ◽  
Ki 67 ◽  
Tissue Samples ◽  
P53 Expression ◽  
Hematoxylin And Eosin

Objective The current study evaluated the expression of WW domain-containing oxidoreductase (WWOX), its association with clinicopathological features and with p53, Ki-67 (cell proliferation) and CD31 (angiogenesis) expression in patients with invasive cervical squamous cell carcinoma (ICSCC). To the best of our knowledge, no other study has evaluated this association. Methods Women with IB stage-ICSCC (n = 20) and women with uterine leiomyoma (n = 20) were prospectively evaluated. Patients with ICSCC were submitted to type B-C1 radical hysterectomy and pelvic lymphadenectomy. Patients in the control group underwent vaginal hysterectomy. Tissue samples were stained with hematoxylin and eosin for histological evaluation and protein expression was detected by immunohistochemistry studies. Results The WWOX expression was significantly lower in the tumor compared with the expression in the benign cervix (p = 0.019). The WWOX expression was inversely associated with the CD31 expression in the tumor samples (p = 0.018). There was no association between the WWOX expression with the p53 expression (p = 0.464) or the Ki-67 expression (p = 0.360) in the samples of invasive carcinoma of the cervix. There was no association between the WWOX expression and tumor size (p = 0.156), grade of differentiation (p = 0.914), presence of lymphatic vascular invasion (p = 0.155), parametrium involvement (p = 0.421) or pelvic lymph node metastasis (p = 0.310) in ICSCC tissue samples. Conclusion The results suggested that WWOX may be involved in ICSCC carcinogenesis, and this marker was associated with tumor angiogenesis.

scholarly journals Temporal analysis of signaling pathways activated in a murine model of two-kidney, one-clip hypertension

2009 ◽  
Vol 297 (4) ◽  
pp. F1055-F1068 ◽  
Author(s):  
Jingfei Cheng ◽  
Wei Zhou ◽  
Gina M. Warner ◽  
Bruce E. Knudsen ◽  
Vesna D. Garovic ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Murine Model ◽  
Proliferative Response ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Nuclear Antigen ◽  
Tubular Atrophy ◽  
Ki 67 ◽  
P53 Expression ◽  
Contralateral Kidney

Unilateral renal artery stenosis (RAS) leads to atrophy of the stenotic kidney and compensatory enlargement of the contralateral kidney. Although the two-kidney, one-clip (2K1C) model has been extensively used to model human RAS, the cellular responses in the stenotic and contralateral kidneys, particularly in the murine model, have received relatively little attention. We studied mice 2, 5, and 11 wk after unilateral RAS. These mice became hypertensive within 1 wk. The contralateral kidney increased in size within 2 wk after surgery. This enlargement was associated with a transient increase in expression of phospho-extracellular signal-regulated kinase (p-ERK), the proliferation markers proliferating cell nuclear antigen and Ki-67, the cell cycle inhibitors p21 and p27, and transforming growth factor-β, with return to baseline levels by 11 wk. The size of the stenotic kidney was unchanged at 2 wk but progressively decreased between 5 and 11 wk. Unlike the contralateral kidney, which showed minimal histopathological alterations, the stenotic kidney developed progressive interstitial fibrosis, tubular atrophy, and interstitial inflammation. Surprisingly, the stenotic kidney showed a proliferative response, which involved largely tubular epithelial cells. The atrophic kidney had little evidence of apoptosis, despite persistent upregulation of p53; expression of cell cycle regulatory proteins in the stenotic kidney was persistently increased through 11 wk. These studies indicate that in the 2K1C model, the stenotic kidney and contralateral, enlarged kidney exhibit a distinct temporal expression of proteins involved in cell growth, cell survival, apoptosis, inflammation, and fibrosis. Notably, an unexpected proliferative response occurs in the stenotic kidney that undergoes atrophy.

Recurrent anaplastic ganglioglioma: pathological characterization of tumor cells

1996 ◽  
Vol 84 (6) ◽  
pp. 1055-1059 ◽  
Author(s):  
Atushi Sasaki ◽  
Junko Hirato ◽  
Yoichi Nakazato ◽  
Masaru Tamura ◽  
Hirotaka Kadowaki
Keyword(s):  
Tumor Cells ◽  
Glial Cells ◽  
Organizer Region ◽  
Nucleolar Organizer Region ◽  
Nucleolar Organizer ◽  
Left Frontal Lobe ◽  
Ki 67 ◽  
Content Type ◽  
Initial Tumor ◽  
Mib 1

✓ A total resection of a left frontal lobe tumor in a 26-year-old man revealed differentiated ganglioglioma with small foci of atypical glial cells exhibiting mild atypia. Six and one-half years later, a large, well-demarcated tumor recurred; at that time, histological analysis revealed both typical ganglioglioma and highly cellular anaplastic areas, the latter predominating. Although the patient subsequently underwent total and subtotal resections, radiation therapy, and chemotherapy, tumors continued to recur at progressively shorter intervals and he died at the age of 35 years. Biopsies of tissue obtained at the last three resections and the autopsy revealed only anaplastic tumor cells. Routine histological examinations indicated that these tumors were uniformly composed of undifferentiated cells. However, pathological studies using immunohistochemical analysis, electron microscopy, and immunoblot analysis demonstrated that a small number of recurrent anaplastic cells had astrocytic features. Results of Ki-67/MIB-1 labeling and silver nucleolar organizer region counts for those cells were high for glial tumors. A retrospective study of the initial tumor showed slightly high MIB-1 labeling for atypical glial cells. This case is characterized by pathological findings of recurrent tumors that correspond to an unusual form of malignant glioma exhibiting slight astrocytic differentiation. The present case suggests that a longer follow-up period (> 5 years) is necessary in cases of ganglioglioma with mild atypia and that careful examinations, including proliferating potential analysis of initial tumor cells, could be important for the diagnosis and treatment of ganglioglioma.

scholarly journals Prognostic Significance of RAS Mutations and P53 Expression in Cutaneous Squamous Cell Carcinomas

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 751 ◽  
Author(s):  
Manuel António Campos ◽  
Sofia Macedo ◽  
Margarida Sá Fernandes ◽  
Ana Pestana ◽  
Joana Pardal ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Clinicopathological Parameters ◽  
P53 Overexpression ◽  
P53 Expression ◽  
Genetic Profiling ◽  
Ras Mutations ◽  
Logistic Regression Models ◽  
Pattern Of Invasion

TP53 is considered the most commonly-altered gene in cutaneous squamous cell carcinoma (cSCC). Conversely, RAS mutations have been reported in a low percentage of cSCC. The objective of our study was to evaluate the frequency of p53 expression and RAS mutations in cSCC and correlate them with clinicopathological features and patient outcome. We performed immunohistochemistry for p53 and genetic profiling for RAS mutations in a retrospective series of cSCC. The predictive value of p53 expression, RAS mutations, and clinicopathological parameters was assessed using logistic regression models. The overall frequency of RAS mutations was 9.3% (15/162), and 82.1% of the cases (133/162) had p53 overexpression. RAS mutations rate was 3.2% (1/31) of in situ cSCCs and 10.7% (14/131) of invasive cSCCs. RAS mutations were more frequently associated with an infiltrative than an expansive pattern of invasion (p = 0.046). p53 overexpression was a predictor of recurrence in the univariate analysis. Our results indicate that RAS mutations associate with features of local aggressiveness. Larger studies with more recurrent and metastatic cSCCs are necessary to further address the prognostic significance of p53 overexpression in patients’ risk stratification.

Progesterone and estrogen receptors in meningiomas: prognostic considerations

1997 ◽  
Vol 86 (1) ◽  
pp. 113-120 ◽  
Author(s):  
Dora W. Hsu ◽  
Jimmy T. Efird ◽  
E. Tessa Hedley-Whyte
Keyword(s):  
Mitotic Index ◽  
Hormone Receptors ◽  
Univariate Analysis ◽  
Inverse Correlation ◽  
Tumor Grade ◽  
Steroid Hormone Receptors ◽  
Nuclear Staining ◽  
Primary Tumors ◽  
Content Type ◽  
The Mean

✓ Meningiomas often contain steroid hormone receptors, but the correlation of receptor presence with patient outcome or mitotic index is unclear. Intracranial meningiomas from 70 patients (27 males and 43 females, mean age 52.9 + 1.7 years [mean ± standard error of the mean], range 15–78 years) were evaluated immunocytochemically for female sex hormone receptors using specific monoclonal antibodies. Prognostic correlations were determined using statistical analyses that included clinical and histological variables. Twenty-eight tumors were benign, 27 had atypical features, and 15 were malignant. Thirty tumors were meningotheliomatous, 11 were fibroblastic, 28 were transitional, and one was secretory. Twenty-nine of the 70 primary tumors recurred (mean interval to recurrence 50.1 ± 10 months). The mean progression-free follow-up period for patients without recurrence was 82.1 ± 7.7 months. Nuclear staining for the progesterone receptor (PR) was found in 58 cases (83%) and PR status was scored as 0 (0% nuclei positive), 1 (< 1%), 2 (1–9%), 3 (10–49%), or 4 (> 50%). Only six tumors (8.6%) contained nuclear estrogen receptor (ER) staining, which was limited to a small number of nuclei (< 1%). Fisher's exact test (two-tailed) showed an inverse correlation between tumor grade and PR staining score (p ≤ 0.001), with 96% of benign and 40% of malignant meningiomas containing PR-positive nuclei. No correlation between age or histological subtype and PR score was detected. Meningiomas from female patients had more PRs (p ≤ 0.05). Analysis of variance revealed that the mitotic index (total counts of mitoses per 10 high-power fields) for tumors with 0 PR staining (18 ± 4.4) was higher (p ± 0.0001) than for those with PR scores of 1 to 4 (4.3 ± 1.9, 5.1 ± 2, 2.2 ± 0.8, and 1.7 ± 0.9, respectively). Univariate analysis indicated that the absence of PR, high mitotic index, and higher tumor grade were significant factors for shorter disease-free intervals. Multivariate analysis showed that a three-factor interaction model, with a PR score of 0, mitotic index greater than 6, and malignant tumor grade, was a highly significant predictor (p ≤ 0.0001) for worse outcome in patients harboring meningiomas. These data indicate that the presence of PRs, even in a small number of tumor cells, is a favorable prognostic factor for meningiomas.

Prognostic factors in intracranial ependymomas in children

2000 ◽  
Vol 93 (4) ◽  
pp. 605-613 ◽  
Author(s):  
Dominique Figarella-Branger ◽  
Muriel Civatte ◽  
Corine Bouvier-Labit ◽  
Joany Gouvernet ◽  
Danielle Gambarelli ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Tumor Removal ◽  
Ki 67 ◽  
Content Type ◽  
Adjuvant Therapies ◽  
Endothelial Proliferation ◽  
Fine Print

Object. The occurrence of intracranial ependymomas in children is relatively infrequent, and their prognostic factors are still controversial, especially regarding histological composition.Methods. A retrospective study was conducted of 37 children treated during the last 20 years for intracranial ependymomas at the Hôpital de la Timone. Both univariate and multivariate statistical analyses were performed to assess the prognostic relevance of patient age and sex, extent of tumor removal, location of the tumor (supratentorial compared with infratentorial, median compared with lateral), tumor histological composition, and adjuvant therapies in affecting the 5-year progression-free survival (PFS) rate and overall survival (OS) rate. The following histopathological features, either alone or in combination, were analyzed: endothelial proliferation, necrosis, loss of differentiating structures (present compared with absent), the number of mitotic figures per 10 hpf, and cellularity (number of nuclei/5 hpf). In addition, immunohistochemical detection of Ki-67 antigen was performed and the Ki-67 labeling index (LI) evaluated in all cases.The 5-year OS and PFS rates were 45% and 25%, respectively (median follow up 34 months). Four patients died of disease without remission (median 163 days) and disease in 21 patients relapsed: 18 in situ and three both in situ and distantly. On univariate analysis total surgical resection and median infratentorial location were associated with a better outcome (p < 0.002) for both OS and PFS. Loss of differentiating structures was associated with poor prognosis (p < 0.008) and the combination of necrosis, endothelial proliferation, and mitotic index greater than 5 was also a negative predictive factor for both OS (p < 0.002) and PFS (p = 0.02). The PFS time was shorter in patients younger than 4 years of age and in patients in whom a Ki-67 LI greater than 1 was found (p = 0.03 and 0.006, respectively). Adjuvant radiotherapy and chemotherapy were not relevant to prognosis. Moreover, among the 15 patients in whom total excision was achieved, OS was better in those who did not receive adjuvant therapies. In contrast, adjuvant therapies significantly enhanced PFS time in patients in whom tumor excision was incomplete.Conclusions. This study and analysis of the literature further highlight that total tumor removal is the treatment of choice for ependymomas in children. Postoperative measurement of residual tumor is required, especially because a subgroup of patients might be treated by surgery alone. Median infratentorial ependymomas have to be distinguished from the lateral type. Appropriate and reproducible histological parameters and Ki-67 LI are of interest as predictors of outcome.

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