Index For Squamous Cell Carcinoma Research Articles

Clinical significance of CD34, podoplanin and Ki-67 expression in patients with locally advanced squamous cell cervical carcinoma

The aim of the study was to assess immunohistochemical CD34, podoplanin and Ki-67 expression in cervical tumour of patients with cervical squamous cell carcinoma (SCC) staged IIB and IIIB, a relationship with selected clinical and histological parameters and its prognostic significance. This prospective study included 52 patients. Microvessel density (MVD) by CD34, lymphatic vessel density (LVD) by podoplanin and the Ki-67 index in specimens from paraffin blocks with cervical SCC tissues were examined. The relationship between these data and selected clinical and histological parameters was analysed. Positive correlation of MVD and the Ki-67 index was observed. No correlation was observed for MVD, LVD and the Ki-67 index in the tumour with staging, grading, length of treatment and squamous cell carcinoma antigen (SCC-Ag) concentration before and after treatment. The expression of MVD, LVD and the Ki-67 index in cervical SCC did not contribute to the risk of relapse and cancer-related death. No relationship was found for MVD, LVD and the Ki-67 index in cervical tumour of patients with locally advanced cervical SCC with staging, grading and serum SCC-Ag level. MVD, LVD and the Ki-67 index in the tumour did not contribute to the risk of relapse or cervical SCC-related death. Impact Statement What is already known on this subject? In many patients, invasive cervical squamous cell carcinoma (SCC) is diagnosed in a locally advanced stage, when the prognosis depends on many well-known factors connected with tumour biology, staging and general condition of the patient. Despite numerous studies, the value of immunohistochemical CD34, podoplanin and Ki-67 expression in cervical tumour of these patients is still not well defined. What do the results of this study add? In our prospective study, no relationship for microvessel density (MVD), lymphatic vessel density (LVD) and the Ki-67 index in cervical tumour of patients with locally advanced cervical SCC with staging, grading and serum squamous cell carcinoma antigen (SCC-Ag) level was found. Additionally, MVD, LVD and the Ki-67 index in the tumour did not contribute to the risk of relapse or cervical SCC-related death. What are the implications of these findings for clinical practice and/or further research? Our study underlines the limited value of immunohistochemical CD34, podoplanin and Ki-67 expression in cervical tumour of patients with locally advanced cervical SCC. Further research should be focussed on identifying and validating novel prognostic and predictive factors.

Effectiveness of (Ki-67) a Cell Proliferative Marker for Distinguishing Overlapping Skin Lesions

Background: it has been always a challenge to differentiate keratoacanthoma (KA) from squamous cellcarcinoma (SCC) and trichoepithelioma (TE) from Basal Cell Carcinoma (BCC). K-i67, a nuclear marker, isa protein whose expression is strictly related to cell proliferation. Therefore, this can be used as an excellentproliferative marker to differentiate between benign and malignant skin lesions.Aim of the Current Study: this study was conducted to investigate the quantitative differences in nuclearexpression of the proliferative index (Ki-67) in SCC, KA, BCC and TE.Materials and Methods: A cross-sectional study enrolling 65 patients selected from private dermatologicaloutpatients clinics at Ibn-Sina Teaching Hospital, Mosul, Iraq diagnosed clinically by dermatologists asBCC, SCC, KA, and TE during the period from Jan 2019- Jan 2020. Their biopsies were sent for routinehistopathological study and additional Immunohistochemical staining using a Ki-67 marker.Results: Ki- 67 expression was seen in all cases ranging in intensity between 3-70%. Moderate expressionwas noticed in (79%) of BCC cases whereas (43%) of well-differentiated SCC cases had mild expression.Quite the reverse, the intensity of Ki-67 immunostaining ranged from 1-20% and 1-5% in KA and TErespectively.Conclusion: Ki-67 can be used as a significant biological marker to differentiate between benignity andmalignancy of overlapping

Progressive increasing in the risk of second and subsequent malignant tumors in patients with a head and neck cancer: A validation study with SEER data.

5595 Background: Patients with a head and neck squamous cell carcinoma (HNSCC) index tumor have a increased risk (2-4% per year) for appearance of a second malignant neoplasms (SMN) and higher risk for successive malignant tumors during the follow-up. The objective of our study was to validate this concept with data of patients included in the Surveillance Epidemiology and End Results (SEER) program (1973-2008). Methods: We performed a population-based cohort study of 149.328 patients with a primary oral cavity, oropharynx, hypopharynx and larynx squamous cell carcinoma index tumor, included in the SEER program, to analize the actuarial survival-free of second and successive tumors. A total of 11.948 (8%) patients had one or more malignant tumors before the diagnosis of HNSCC. Results: During the follow-up period, a total of 31.507 new SMN appeared. There was a progressive and significant increase in the risk of SMN. The annual hazard ratio for 2nd to 7th successive SMN was 2.3%, 2.7%, 3.9%, 5.4%, 8.9% and 19.1% annual risk respectively. Additionally 11 patients had 8th SMN. We observed a progressive increase in the risk of appearence of new malignant tumors located in and outside the aerodigestive tract. The increase in the risk of SMN was higher for tumors located in the aerodigestive tract than tumors located outside aerodigestive tract. It was a tendency towards the increase in the proportion of HNSCC with the appearance of new tumors, with a decrease in the proportion of the malignant tumors located in the lung and in locations outside the aerodigestive tract. There were significant differences inthe risk of SMN between second and third, third and fourth, fourth and fifth, and sist and seventh tumors (p<0.0001). Conclusions: In patients with HNSCC there is a progressive increase in the risk of appearance of successive tumors. Previous tobacco and alcohol consumption, persistence in the exposure to carcinogens and individual susceptibility (genetic) could play a role in the increased risk of SMN. We have validated this concept with data from the SEER program.

Immunohistochemical Comparative Analysis of Cell Proliferation and Angiogenic Index in Squamous Cell Carcinomas of the Tongue Between Young and Older Patients

Oral squamous cell carcinoma (SCC) is a malignant epithelial tumor that is uncommon in individuals younger than 45 years. This study compared the cell proliferation and angiogenic index in SCCs of the tongue between young and older patients. Forty SCCs of the tongue, 20 diagnosed in young patients (≤ 40 y) and 20 diagnosed in older patients (>50 y) were evaluated by immunohistochemistry. Cell proliferation was evaluated using the Ki-67 labeling index (LI). The angiogenic index was determined by microvessel count (MVC) using anti- von Willebrand factor antibody. The mean Ki-67 LI in SCCs of the tongue was 43.8% (range, 26.0% to 72.4%) in young patients and 42.5% (range, 9.0% to 59.4%) in older patients (P=0.968). No significant difference in the Ki-67 LI was observed in relation to clinical stage or histologic grade of malignancy in either group (P>0.05). The mean MVC in SCCs of the tongue was 24.3 (range, 8.6 to 51.6) in young patients and 25.6 (range, 5.4 to 42.4) in older patients (P=0.543). There was no significant difference in MVC in relation to clinical stage or histologic grade of malignancy in either group (P>0.05). In addition, no significant correlation was observed between the Ki-67 LI and the angiogenic index (P>0.05). The results of this study suggest that the more aggressive biological behavior of SCC of the tongue in young patients may not be related to a higher cell proliferation rate or a higher angiogenic index.

Stromal CD10 expression, as well as increased dermal macrophages and decreased Langerhans cells, are associated with malignant transformation of keratinocytes

It has become evident that resident stromal cells, such as fibroblasts and inflammatory cells, are involved in the metastatic process, including proliferation or migration of malignant neoplasms. We analyzed CD10+ stromal cells, dermal macrophages and Langerhans cells (LCs) in skin tumors. Immunohistological staining was performed with markers for macrophages (CD68), LC (CD1a), stromal fibroblasts (CD10) and cell proliferation (Ki67) in 12 normal skins (NSs) and 15 cases each of seborrheic keratosis (SK), actinic keratosis (AK), keratoacanthoma (KA), Bowen's disease (BD) and squamous cell carcinoma (SCC). All SCCs showed weak to strong stromal CD10 expression, while all NS, SK and AK were negative. Weak CD10 expression was observed in only 2 of 15 samples in both BD and KA. The number of CD68+ cells and Ki67 labeling index in SCC and BD were significantly higher than that in KA, AK and SK. In contrast, the number of LC was lower in SCC and BD. The stromal CD10 expression was significantly correlated with the Ki67 labeling indices and CD68+ cells and negatively correlated with decreased LC. The stromal CD10 expression is associated with malignant transformation of keratinocytes together with infiltration of dermal macrophages and loss of LC.

Prognostic Significance of New Immunohistochemistry Scoring of p53 Protein Expression in Cutaneous Squamous Cell Carcinoma of Mice

This study was conducted to investigate the prognostic value and therapeutic response of treatment modalities on p53 protein expression and AgNOR index in squamous cell carcinoma (SCC). Furthermore, based on data, we proposed a new p53 immunohistochemistry (IHC) scoring system. Sixty albino mice were given 7,12-dimethylbenz[a]anthracine (DMBA) and 12-O-tetradecanoly Phorbol-13-acetate (TPA) to produce skin tumors. The retinoids were given after the development of tumors. p53 immunohistochemical and AgNOR staining was performed on the sections taken before and after the retinoid administration. p53 protein was expressed in 31 of the lesions (60.8%). AgNOR index was high in all 51 (100%) of the pretreated lesions. There was a marked decrease in the expression of p53 protein in 16/51 (31.4%) and AgNOR index in 36/51 (70.6%) in post-treated mice. There was no decrease in the expression of both markers in mice harboring malignant neoplasms. p53 IHC scores were 0, I, and II in epidermal hyperplasia, papilloma, and dysplasia, respectively, while they were II, III, IV, and V in SCC in situ, well-differentiated, moderately differentiated, and poorly differentiated SCCs, respectively. Alteration of p53 and AgNOR index occured during the development of SCC. The p53 IHC scores are directly related to the grades of malignancy. Both markers might be used as a supportive tool with routinely performed Hematoxylin and Eosin staining and may help in the diagnosis of SCC. The newly proposed p53 IHC scoring system will help histopathologists in making their differential diagnosis among benign, premalignant, and malignant lesions. It will also help the oncologists to assess the prognosis and effectiveness of their chemotherapy.

Combination therapy with 2‐difluoromethylornithine and a polyamine transport inhibitor against murine squamous cell carcinoma

Using a recently developed autochthonous mouse model of squamous cell carcinoma (SCC), a combination therapy targeting polyamine metabolism was evaluated. The therapy combined 2-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), and MQT 1426, a polyamine transport inhibitor. In 1 trial lasting 4 weeks, combination therapy with 0.5% DFMO (orally, in the drinking water) and MQT 1426 (50 mg/kg i.p., bid) was significantly more effective than with either single agent alone when complete tumor response was the endpoint. In the combination group, 72% of SCCs responded completely vs. 21 and 0% for DFMO and MQT 1426, respectively. A second trial involved a 4-week treatment period followed by 6 weeks off-treatment. With apparent cures as an endpoint, combination therapy was again more effective than either agent alone: a 50% apparent cure rate was observed in the combination group vs. 7.7% in the DFMO group. MQT 1426 had no inhibitory effect on SCC ODC activity nor did it enhance the inhibition by DFMO, but SCC polyamine levels declined more rapidly when treated with combination therapy vs. DFMO alone. The apoptotic index in SCCs was transiently increased by combination therapy but not by DFMO alone. Thus, targeting both polyamine biosynthesis and polyamine transport from the tumor microenvironment enhances the efficacy of polyamine-based therapy in this mouse model of SCC.

Prognostic impact of p53, c-erbB-2 and epidermal growth factor receptor on head and neck carcinoma

p53, c-erbB-2 and epidermal growth factor receptor (EGFR) are cancer-related proteins that are usually expressed in head and neck squamous cell carcinoma (SCC). Their prognostic value remains controversial. To evaluate the prognostic impact of p53, c-erbB-2 and EGFR expression in head and neck SCC. Prospective. Head and Neck Surgery Department, Hospital AC Camargo, São Paulo. Fifty-four patients were studied for p53, c-erbB-2 and EGFR expression in head and neck SCC and adjacent mucosa, via immunohistochemistry. These data were correlated with histoclinical data and survival. There was a direct association of p53 expression in SCC and mucosa (p = 0.001); loss of c-erbB-2 expression (-) from normal mucosa to SCC (p = 0.04); lower frequency of association of c-erbB-2 (+) with EGFR (-) in SCC (p = 0.02); and a direct association of EGFR (+) expression in SCC and mitotic index (p = 0.03). The 60-month actuarial survival rates for patients presenting lymph node metastasis were higher when there was no capsule rupture by SCC (48.3%; p = 0.02), no more than one positive lymph node (52.3%; p = 0.004) or clear surgical margins (47.0%; p = 0.01), in comparison with patients presenting capsule rupture (20.2%), two or more positive lymph nodes (18.7%) or compromised surgical margins (0.0%), respectively. Patients presenting SCC p53 (+) and EGFR (-) demonstrated greater survival (75.0%; p = 0.03) than for the remaining group (33.1%). Multivariate analysis confirmed the positive impact of p53 (+) and EGFR (-) on survival (p = 0.02). Associations were found for p53, c-erbB-2 and EGFR expression with histoclinical data and prognosis. Interestingly, these results suggest that loss of mucosal c-erbB-2 expression could be involved in SCC carcinogenesis; EGFR expression in SCC is related to tumor mitotic index; and presence of p53 with absence of EGFR expression in head and neck SCC may be a prognostic factor for survival. Further prospective studies should be conducted to confirm the influence of p53, c-erbB-2 and EGFR on histoclinical data and prognosis.

741 Evaluation of the KI-67 labelling index for squamous cell carcinoma of the penis

741 Evaluation of the KI-67 labelling index for squamous cell carcinoma of the penis

Inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters by tea and curcumin.

Tea is one of the most popular beverages consumed in the world. Curcumin, the major yellow pigment in turmeric, is used widely as a spice and food-coloring agent. In this study, we studied the effects of tea and curcumin on 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters. DMBA solution (0.5% in mineral oil, 0.1 ml) was applied topically to the left cheek pouch of male Syrian golden hamsters 3 times/week for 6 weeks. Two days after the last treatment of DMBA, the animals received green tea (6 mg tea solids/ml) as drinking fluid, or 10 mmol curcumin applied topically 3 times/week, or the combination of green tea and curcumin treatment, or no treatment for 18 weeks. The combination of tea and curcumin significantly decreased the oral visible tumor incidence from 92.3% (24/26) to 69.2% (18/26) and the squamous cell carcinoma (SCC) incidence from 76.9% (20/26) to 42.3% (11/26). The combination of tea and curcumin also decreased the number of visible tumors and the tumor volume by 52.4 and 69.8%, as well as the numbers of SCC, dysplasic lesions and papillomas by 62.0, 37.5 and 48.7%, respectively. Green tea or curcumin treatment decreased the number of visible tumors by 35.1 or 39.6%, the tumor volume by 41.6 or 61.3% and the number of SCC by 53.3 or 51.3%, respectively. Green tea also decreased the number of dysplasic lesions. Curcumin also significantly decreased the SCC incidence. Tea and curcumin, singly or in combination, decreased the proliferation index in hyperplasia, dysplasia and papillomas. Only the combination treatment decreased the proliferation index in SCC. Tea alone and in combination with curcumin significantly increased the apoptotic index in dysplasia and SCC. Curcumin, alone and in combination with tea, significantly inhibited the angiogenesis in papilloma and SCC. The results suggested that green tea and curcumin had inhibitory effects against oral carcinogenesis at the post-initiation stage and such inhibition may be related to the suppression of cell proliferation, induction of apoptosis and inhibition of angiogenesis.

Changes of Ki-67 index in squamous cell carcinoma of the cervix during the early course of radiotherapy and prediction of radiotherapy response

Purpose: To determine whether the changes of Ki-67 index during the early course of radiotherapy could predict the response to treatment in squamous cell carcinoma of the uterine cervix and would be of value in clinical practice.

141Apoptotic/mitotic ratio — A possible prognostic index for squamous cell carcinoma of the head and neck treated with radiotherapy

141Apoptotic/mitotic ratio — A possible prognostic index for squamous cell carcinoma of the head and neck treated with radiotherapy

Labeling index in squamous cell carcinoma of the larynx

Two cell kinetic parameters, the 3H-thymidine labeling index (TLI) and the mitotic index (MI), were studied in vitro on fragments of squamous cell carcinoma tissue of the larynx. They were evaluated to identify those elements able to characterize the growth of these solid tumors. The values of these parameters were analyzed as a function of the clinical stage and the involvement of the regional lymph nodes. Results showed a statistically significant increase in the TLI from stage T1 to T3. No statistically significant differences in the TLI values were observed between the patients with positive and negative lymph nodes.

Variability of the thymidine labeling index in squamous cell carcinoma of the head and neck.

Tritiated thymidine (3HTdR) labeling is the standard technique for determining the kinetic activity of tumors. This method has been used to label multiple sections of tumor specimens obtained from seven patients with advanced squamous cell carcinoma of the head and neck. Considerable variability was observed in the labeling index in different sites from the same specimen. To reduce the large sampling error due to heterogeneity, we recommend that an average value be determined from multiple sections when employing this technique.