Printer Friendly

CORRELATION OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) AND Ki-67 EXPRESSION WITH HISTOLOGICAL GRADE AND STAGE OF RENAL CELL CARCINOMA.

BACKGROUND

Renal cell carcinoma (RCC) is the most common malignant kidney tumour in adults. Worldwide, it is the 9th most common cancer in men and 14th in women. [1] The case fatality rate is lower in highly developed countries than in countries with low or medium levels of socioeconomic development. It is the 3rd leading cause of death among urologic tumours and is resistant to chemotherapy and radiotherapy. [2-3] However, there has been a huge development in effective molecular targeted therapies in past few years for specific types of RCC with different histology and molecular abnormalities.

Therefore, accurate histological diagnosis and classification have become increasingly important in these cases. [4] Among renal cell tumours, common malignant varieties are Clear Cell Renal Cell Carcinoma (CCRCC), Papillary Renal Cell Carcinoma (PRCC) and Chromophobe Renal Cell Carcinomas (ChRCC). Usually histological diagnosis of renal tumours can be done easily by routine Haematoxylin and eosin (H&E) stain. However, immune markers have become essential in several contexts which include differentiating renal and non-renal neoplasm and sub-typing of RCCs. [5] Symptoms of all types of kidney tumours are very similar and nonspecific. Most common is the triad of symptoms including painless hematuria, palpable mass or abdominal lump and flank pain. [1] But different histologic subtypes are known to have distinct prognosis. It has been very challenging to predict the prognosis of each of the patients with RCC. Classic prognostic factors, staging and grading were also not always very helpful. [6] So there has been a definite need for better tools in predicting the clinical course of RCC in this era of molecular targeted therapies.

Angiogenesis is important in determining tumour progression and development of metastases. [7] Vascular endothelial cell growth factor (VEGF) is one of the key players of angiogenesis and it has a role in promoting proliferation, survival, and migration of endothelial cells. VEGF helps in new vessel formation in tumours by acting as a chemoattractant for bone marrow derived progenitor cells. [8-9] It has been documented in numerous studies that higher VEGF-A levels correlate with high vascular density, higher proliferation rate, higher nuclear grade and advanced tumour stage resulting in poor clinical outcome. [10] Recent developments in our understanding of the molecular pathways controlling tumour angiogenesis have led to the development of novel VEGF-targeting agents for treatment of RCCs. [11]

Proliferation index as determined by Ki-67 is known to be of prognostic importance and is known to correlate with tumour grade in RCCs. Ki-67 is a non-histone protein that is usually found in all the phases of cell cycle (G1, S, G2 and mitosis) while it is absent in nondividing cells (G0). [12] This property makes it an excellent marker for determining the proliferating activity of tumour cells.

Here we performed an institution-based study on nephrectomy specimens which were histologically diagnosed as RCC and applied IHC to correlate VEGF and Ki-67 expression with grade and stage of RCC and compare VEGF expression and Ki-67 labelling index, if any and also discussed their possible utility as tissue-based biomarkers.

MATERIALS AND METHODS

Study Design

Cross-sectional observational study.

Specimens and General Information

A total of 50 specimens of RCCs were studied which were collected from patients undergoing total and partial nephrectomy in the department of Urosurgery of a tertiary care institute in eastern India from February 2017 to July 2018. Sample size was taken based on the convenience of the study. It was a cross-sectional observational study. Histologically diagnosed RCCs were included in the study and renal tumours other than RCCs were excluded from the study.

Histopathological Examination

Grossing and reporting of total and partial nephrectomy specimens with RCCs were done according to CAP (College of American Pathologists) protocol [13] which is based on AJCC/UICC TNM, 8th edition. [14] Specimens were fixed in 10% neutral buffered formalin. Representative areas were sampled, and histopathological examination was done following proper tissue processing, paraffin embedding and staining with haematoxylin-eosin (H&E) respectively. After histological confirmation of diagnosis of RCC, following parameters were analysed: histological type, tumour grade, lymphovascular and perineural invasion, necrosis, sarcomatoid or rhabdoid differentiation and staging. Specific histologic subtype was assigned according to WHO 2016 classification of tumours of the Urinary System and Male Genital Organs [1]. Histologic grading of tumours was done according to WHO/ International Society of Urological Pathology (WHO/ISUP) [1] grading system for CCRCC and PRCC. Chromophobe carcinomas could not be graded using this system. (Figure 1) Pathologic (pTNM) staging was done according to American Joint Committee on Cancer 2010. [14]

Immunohistochemistry (IHC) for VEGF and Ki-67

Immunohistochemistry was performed on 3[micro] sections taken on poly-L-Lysine coated slides. Primary antibodies which were used for detection of VEGF and Ki-67 are as follows-Ki-67: Monoclonal Mouse Anti-Human, RTU, clone MIB-1, Novocastra, Leica.

VEGF: Monoclonal rabbit antibody, RTU, clone: RBT-VEGF, Bio SB. Di-amino benzidine (DAB) was used as chromogen. Positive controls which were used are as follows- (1) Lobular capillary haemangioma for VEGF (2) Tonsil for Ki-67. Negative control was achieved by omitting primary antibody.

Evaluation of IHC Staining:

For quantitative analysis of Ki-67, first hot spots were determined using low power and then approximately 1000 cells were counted in 5 high power fields. Only nuclear staining was considered positive and staining intensity was not assessed. Ki-67 index was expressed as percentage of positive staining cells among total number of invasive cells in the area scored. We used our own laboratory cut-off value of 15% according to Mehdi MZ et al. [15] For VEGF, staining was determined semiquantitatively according to a three-grade scale according to Yildiz E et al [16]:

* 0: no staining of tumour cells;

* 1+: membranous stain with no cytoplasmic immunostaining or with light cytoplasmic staining of some tumour cells (<50%);

* 2+: diffuse and strong membranous and cytoplasmic staining of most tumour cells (>50%).

Statistical Analysis

Statistical Analysis was performed with help of Epi Info (TM) 7.2.2.2 which is a trademark of the Centers for Disease Control and Prevention (CDC). Using this software, basic cross-tabulation and frequency distributions were prepared. [chi square] test was used to test the association between different variables under study. Corrected [chi square] test was used in case if any one of cell frequency was found less than 5 in bivariate frequency distribution. T-test was used to compare two means. Diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value were calculated to compare the findings of different diagnostic tools. p [less than or equal to] 0.05 was considered statistically significant.

RESULTS

A total of 50 cases of renal cell carcinoma were studied. The average age of patients at the time of diagnosis was estimated to be 52.52 [+ or -] 9.32 years with range 35-73 years and the median age was 51 years. Most of the patients (72.0%) were of in age group 40 - 59 years which was significantly higher than other age group (p<0.001) of which 88.0% patients were males, 68.0% patients having a history of cigarette smoking. 60.0% patients were hypertensive and 52.0% were obese. 60.0% of cases had right sided disease.

According to WHO/ISUP [1] grading system, 12.5% of the tumours were grade 1, 33.3% grade 2, 25.0% grade 3 and 29.2% grade 4. There were 20.0% cases of stage I, 28.0% cases of stage II, 50.0% cases of stage III and 2% cases of stage IV disease respectively. Necrosis was found among 62.0% cases. 18.0% cases showed sarcomatoid differentiation whereas 4.0% cases showed rhabdoid differentiation. Among the 50 cases, 22 (44.0%) showed microscopic evidence of lymphovascular space invasion (LVSI), and 6 (12.0%) presented with microscopic evidence of perineural invasion (PNI).

Distribution of Renal Cell Carcinomas According to Histological Diagnoses and Expression of VEGF and Ki-67 in Various Sub-Types

Out of the 50 cases studied, 43 cases were CCRCC, 5 cases were PRCC and 2 cases were ChRCC. For CCRCC, most of the tumours (44.2%) were VEGF Grade-1 with 41.9% Grade-2 tumours and 14% of Grade-0 tumours. For ChRCC one tumour was negative for VEGF (grade 0) and one tumour was VEGF grade 1. No case with Grade-2 was found. For PRCC the VEGF grades were Grade-0 in most of the cases (60.0%). (Figure 2)

For CCRCC, Ki-67 labelling index was [greater than or equal to] 15% in most of the cases (60.5%). For ChRCC all the cases were with Ki-67 labelling index<15% (100.0%). For PRCC, Ki-67 labelling index was <15% in most of the cases (80.0%). (Figure 3)

There was no significant association between VEGF grades and histological types of RCC (p=0.10). Ki-67 labelling index showed no significant association with histological type of tumours. (p=0.067)

Correlation of VEGF Grade with Grade and Stage of RCCs:

Out of 10 stage-I tumours, 8 cases showed VEGF expression as grade 0, 1 case showed VEGF expression as grade 1 and 1 case showed VEGF expression as grade 2. Out of 14 stage-II tumours, 2 cases showed VEGF expression as grade 0, 8 cases showed VEGF expression as grade 1 and 4 cases showed VEGF grade 2. Out of 25 stage-III tumours, no case showed VEGF expression as grade 0, 12 cases showed VEGF expression as grade 1 and 13 cases showed VEGF expression as grade 2. We found only one case of stage IV tumour which was VEGF grade 2. So, we found that VEGF grades showed significantly increasing trend with the increase in stage of the tumours, which was statistically significant (p<0.00001).

Out of 6 Grade 1 tumours, 4 cases showed VEGF expression as grade 0, 2 cases showed VEGF expression as grade 1 and no case showed VEGF expression as grade 2. Out of 16 grade 2 tumours, 5 cases showed VEGF expression as grade 0, 11 cases showed VEGF expression as grade 1 and no case showed VEGF expression as grade 2. Out of 12 grade 3 tumours, no cases showed VEGF expression as grade 0, 5 cases showed VEGF expression as grade 1 and 7 cases showed VEGF expression as grade 2. Out of 14 grade 4 tumours, no cases showed VEGF expression as grade 0, 2 cases showed VEGF expression as grade 1 and 12 cases showed VEGF expression as grade 2. So, it was noted that VEGF grades showed significantly increasing trend with the increase in histological grade of the tumours, which was statistically significant. (p<0.00001). (Table 1)

Correlation of Ki-67 Labelling Index with Grade and Stage of RCCs:

Out of 10 stage-I tumours, 9 cases showed Ki-67 labelling index <15% and 1 case showed Ki-67 labelling index [greater than or equal to] 15%. Out of 14 stage-II tumours, 6 cases showed Ki-67 labelling index <15% and 8 cases showed Ki-67 labelling index [greater than or equal to] 15%. Out of 25 stage-III tumours, 8 cases showed Ki-67 labelling index <15% and 17 cases showed Ki-67 labelling index [greater than or equal to] 15%. We found only one case of stage IV tumour which showed Ki67 labelling index [greater than or equal to] 15%. So, it was noted that Ki-67 labelling index showed significantly increasing trend with the increase in stage of the tumours, which was statistically significant (p<0.00001).

Out of 6 Grade 1 tumours, all cases showed Ki-67 labelling index <15% and no cases showed Ki-67 labelling index [greater than or equal to] 15%. Out of 16 grade 2 tumours, 15 cases showed Ki-67 labelling index <15% and 1 case showed Ki-67 labelling index [greater than or equal to] 15%. Out of 12 grade 3 tumours, no cases showed Ki-67 labelling index <15% and all cases showed Ki-67 labelling index [greater than or equal to] 15%. Out of 14 grade 4 tumours, no cases showed Ki-67 labelling index <15% and all cases showed Ki-67 labelling index [greater than or equal to] 15%. So, it was noted that Ki-67 labelling index showed significantly increasing trend with the increase in histological grade of the tumours, which was statistically significant. (p<0.00001). (Table 2)

Correlation of VEGF Expression with Presence of LVSI and Necrosis:

Out of 10 VEGF grade 0 tumours, only one case showed presence of LVSI and one case showed presence of necrosis. Out of 21 VEGF grade 1 tumours, 8 cases showed presence of LVSI and 13 cases showed presence of necrosis. Out of 19 VEGF grade 2 tumours, LVSI was present in 13 cases and 17 cases showed presence of necrosis. So, we found significant association between VEGF grade and presence of LVSI and necrosis (p=0.0083). (Table 3)

Correlation and Comparison between VEGF and Ki-67:

Out of 23 tumours in which Ki-67 expression was <15%, 10 tumours were VEGF grade 0, 13 tumours were VEGF grade 1 and no tumours showed expression of VEGF as Grade 2. Out of 27 tumours in which Ki-67 expression was >15%, no tumours were VEGF grade 0, 8 tumours were VEGF grade 1 and 19 tumours showed expression of VEGF as grade 2. So, it was evident that the Ki-67 labelling index showed significantly increasing trend with the increase in VEGF grades of the tumours, which was statistically significant. (p<0.00001) (Table 4)

DISCUSSION

RCC is a well-recognized as a malignant tumour with an unpredictable clinical course. Patients with tumours showing same histological features can show a wide variation in biological behaviour and clinical outcome [17]. Renal cell carcinoma has the poorest prognosis among all the urological tumours. Tumour stage is the most powerful predictor of prognosis. Among histological parameters, WHO/ISUP nuclear grade is considered the most important prognostic parameter but it often shows substantial intra-observer and inter-observer variation. [15]

There are no current immunohistochemical prognostic markers which are routinely used for RCCs. In this era of new treatment possibilities, there is need for better prognostic tools to plan the treatment and follow-up of RCC patients. Proliferation index of RCC as determined by Ki-67 is known to have prognostic importance in univariate and multi-variate analysis and it also correlates with tumour grade. [15] In recent years importance has been given to the expression of different angiogenic factors like VEGF in RCCs. [18]

On this background, we conducted a study to assess VEGF expression and Ki-67 labelling index in RCCs and document the possibility of a correlation between these markers with different known prognostic parameters of RCC by IHC.

In our study, most of the RCC cases were VEGF as grade-1 (42.0%) while 38% cases were VEGF grade-2 and 20% were VEGF grade-0 or with no staining which corroborate with the findings of Ebru T et al [19] who got only 4 cases which did not show staining while 27 cases (37.5%) showed strong VEGF staining.

Yang S et al [20] found VEGF-A expression in 51.5% of RCC cases, which was significantly higher than the rate of expression in normal renal tissue surrounding the carcinoma. We found VEGF expression in 80% of RCC cases. This difference in expression levels may be attributed to diversity in detection techniques and varying sample size.

We also found a significant association of nuclear grade with VEGF expression. This was similar to the studies done by Yildiz E et al, [16] Burgesser M et al [18] and Osman WM et al. [21]

Expression of VEGF grades was seen to increase with the increase in stage of the tumours. This observation was found to be concordant with Ebru T et al, [19] Burgesser M et al [18] and Osman WM et al. [21]

No significant difference was found in our study between different RCC types concerning cytoplasmic VEGF expression which is concordant with findings of Yildiz E et al [16] and Matusan-Ilijas K et al. [22]

Furthermore, we noted that VEGF grade showed significant association with presence of necrosis and lymphovascular invasion which is similar to studies by Fujita N et al [23] and Veselaj F et al. [24]

In our study, we found the mean Ki-67 labelling index (mean [+ or -] s.d.) of the patients was 14.32 [+ or -] 3.88 with a range 5-22 and the median was 15.0. Most of the tumours (54.0%) had Ki-67 labelling index [greater than or equal to] 15% while the rest 46% of cases had Ki-67 labelling index <15%. In the study done by Amouian S et al, [25] out of 30 tumours studied, 20 (66.6%) were positive for Ki67. In the study done by Delahunt B et al, [26] 206 cases were studied, and Ki-67 expression was detected in 83%. Out of 1239 cases studied by Zheng K et al, [27] Ki-67 was detected in 47.7%. However, different authors have used different cut-off values for Ki-67 labelling index.

We also noted that Ki-67 proliferative index increased with increase in nuclear grade. This was similar to the studies done by Wong PK et al, [28] Bui MH et al, [29] Zheng K et al, [27] Amouian S et al [25] and Gelb AB et al, [30] who also found significant association of nuclear grade with Ki-67 labelling index.

In the studies done by Onda H et al, [31] Burgesser M et al [18] and Gayed BA et al [32] respectively, Ki-67 expression was correlated with tumour stage which was concordant with our study.

We found no significant correlation between Ki-67 expression and histologic tumour subtypes. This was similar to the studies conducted by Wong PK et al [28] and Mehdi MZ et al. [15]

In current study, there was significant association between VEGF grades and Ki-67 labelling index of RCCs (p<0.0001). The Ki-67 labelling index showed significantly increasing trend with the increase in VEGF grades of the tumours which was concordant with Burgesser M et al, [18] However, this finding was discordant with Matusan-Ilijas K et al [22] who did not find any association between these markers.

CONCLUSION

Considering the observations of the current study, it can be concluded that the significant increase in VEGF expression and Ki-67 labelling index with tumour stage and grade and other prognostic parameters indicate that these two markers are associated with tumour growth and progression in RCCs. Their combined expression has a beneficial role in prediction of high stage tumours (Stage III/IV) and provides means for determining tumours that will respond to anti-angiogenic therapies. Since our study was limited by time, relatively small numbers of cases and minimum opportunity for follow up, further studies involving large number of cases with proper scope for follow up is needed to validate these results. Last but not the least, a better understanding of molecular pathways involved in pathogenesis and growth of tumours may help in the development of new strategies and target therapies for the early detection and treatment of RCCs.

ACKNOWLEDGMENT

We would like to thank Dr. Ranu Sarkar (Professor and Head of the Department of Pathology, Nil Ratan Sircar Medical College and Hospital) for guiding us throughout the study.

REFERENCES

[1] Humphrey PA, Moch H, Reuter VE, et al. World Health Organization (WHO) Classification of Tumours. Pathology and Genetics of the urinary system and male genital organs. Geneva, Switzerland: WHO Press 2016.

[2] Zacchia M, Vilasi A, Capasso A, et al. Genomic and proteomic approaches to renal cell carcinoma. Journal of Nephrology 2011;24(2):155-64.

[3] Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA: A Cancer Journal for Clinicians 2008;58(2):71-96.

[4] Shen SS, Truong LD, Scarpelli M, et al. Role of immunohistochemistry in diagnosing renal neoplasms: when is it really useful? Archives of Pathology & Laboratory Medicine 2012;136(4):410-7.

[5] Truong LD, Shen SS. Immunohistochemical diagnosis of renal neoplasms. Archives of Pathology & Laboratory Medicine 2011;135(1):92-109.

[6] Crispen PL, Boorjian SA, Lohse CM, et al. Predicting disease progression after nephrectomy for localized renal cell carcinoma: the utility of prognostic models and molecular biomarkers. Cancer: Interdisciplinary International Journal of the American Cancer Society 2008;113(3):450-60.

[7] Berger DP, Herbstritt L, Dengler WA, et al. Vascular endothelial growth factor (VEGF) mRNA expression in human tumour models of different histologies. Annals of Oncology 1995;6(8):817-25.

[8] Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target. Nature 2005;438(7070):967-74.

[9] Rafii S, Lyden D, Benezra R, et al. Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy? Nature Reviews Cancer 2002;2(11):826-35.

[10] Wiesener MS, Munchenhagen PM, Berger I, et al. Constitutive activation of hypoxia-inducible genes related to overexpression of hypoxia-inducible factor-1[alpha] in clear cell renal carcinomas. Cancer Research 2001;61(13):5215-22.

[11] Escudier B, Cosaert J, Pisa P. Bevacizumab: direct anti-VEGF therapy in renal cell carcinoma. Expert Review of Anticancer Therapy 2008;8(10):1545-57.

[12] Gerdes J, Lemke H, Baisch H, et al. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. The Journal of Immunology 1984;133(4):1710-5.

[13] College of American pathologists [certified]: Protocol for the examination of specimens from patients with invasive carcinoma of renal tubular origin [Protocol web posting date: June 2017]. https://www.cap.org/protocols-andguidelines/cancer-reporting-tools/cancer-protocol- templates [Last accessed in October 2018].

[14] American Joint Committee on Cancer (AJCC). AJCC Cancer Staging Manual. 8th edn. New York: Springer 2017.

[15] Mehdi MZ, Nagi AH, Naseem N. MCM-2 and Ki-67 as proliferation markers in renal cell carcinoma: a quantitative and semi-quantitative analysis. International Braz J Urol 2016;42(6):1121-8.

[16] Yildiz E, Gokce G, Kilicarslan H, et al. Prognostic value of the expression of Ki-67, CD44 and vascular endothelial growth factor and microvessel invasion, in renal cell carcinoma. BJU International 2004;93(7):1087-93.

[17] Gettman MT, Blute ML, Spotts B, et al. Pathologic staging of renal cell carcinoma: significance of tumour classification with the 1997 TNM staging system. Cancer 2001;91(2):354-61.

[18] Burgesser M, Riba V, Ojeda SM, et al. Expression of VEGF-A, HIF-1 A, CD34 and Ki67 in clear cell renal cell carcinomas and their relationship with conventional prognostic markers. Revista de la Facultad de Ciencias Medicas 2014;71(1):7-15.

[19] Ebru T, Fulya OP, Hakan A, et al. Analysis of various potential prognostic markers and survival data in clear cell renal cell carcinoma. International Braz J Urol 2017;43(3):440-54.

[20] Yang S, Gao Q, Jiang W. Relationship between tumour angiogenesis and expression of cyclo-oxygenase-2 and vascular endothelial growth factor--A in human renal cell carcinoma. Journal of International Medical Research 2015;43(1):110-7.

[21] Osman WM, Youssef NS. Combined use of COX-1 and VEGF immunohistochemistry refines the histopathologic prognosis of renal cell carcinoma. International Journal of Clinical and Experimental Pathology 2015;8(7):8165-77.

[22] Dorevic G, Matusan-Ilijas K, Babarovic E, et al. Hypoxia inducible factor-1a correlates with vascular endothelial growth factor A and C indicating worse prognosis in clear cell renal cell carcinoma. Journal of Experimental & Clinical Cancer Research 2009;28(1):40.

[23] Fujita N, Okegawa T, Terado Y, et al. Serum level and immunohistochemical expression of vascular endothelial growth factor for the prediction of postoperative recurrence in renal cell carcinoma. BMC Research Notes 2014;7(1):369.

[24] Veselaj F, Manxhuka-Kerliu S, Neziri A, et al. Prognostic value of vascular endothelial growth factor A in the prediction of the tumour aggressiveness in clear cell renal cell carcinoma. Open Access Macedonian Journal of Medical Sciences 2017;5(2):167-72.

[25] Amouian S, Farzadnia M, Memar B, et al. Expression of P53 and Ki67 proteins in renal cell carcinoma and its relationship with nuclear grade. Iranian Journal of Pathology 2008;3(1):25-9.

[26] Delahunt B, Bethwaite PB, Thornton A, et al. Proliferation of renal cell carcinoma assessed by fixation-resistant polyclonal Ki-67 antibody labeling. Correlation with clinical outcome. Cancer 1995;75(11):2714-9.

[27] Zheng K, Zhu W, Tan J, et al. Retrospective analysis of a large patient sample to determine p53 and Ki67 expressions in renal cell carcinoma. J BUON 2014;19(2):512-6.

[28] Wong PK, Lee ST, Murone C, et al. In vivo imaging of cellular proliferation in renal cell carcinoma using 18F-fluorothymidine PET. Asia Oceania Journal of Nuclear Medicine and Biology 2014;2(1):3-11.

[29] Bui MH, Visapaa H, Seligson D, et al. Prognostic value of carbonic anhydrase IX and KI67 as predictors of survival for renal clear cell carcinoma. The Journal of Urology 2004;171(6 Pt 1):2461-6.

[30] Gelb AB, Sudilovsky D, Wu CD, et al. Appraisal of intratumoural microvessel density, MIB-1 score, DNA content, and p53 protein expression as prognostic indicators in patients with locally confined renal cell carcinoma. Cancer: Interdisciplinary International Journal of the American Cancer Society 1997;80(9):1768-75.

[31] Onda H, Yasuda M, Serizawa A, et al. Clinical outcome in localized renal cell carcinomas related to immunoexpression of proliferating cell nuclear antigen, Ki-67 antigen, and tumour size. Oncology Reports 1999;6(5):1039-43.

[32] Gayed BA, Youssef RF, Bagrodia A, et al. Ki67 is an independent predictor of oncological outcomes in patients with localized clear-cell renal cell carcinoma. BJU International 2014;113(4):668-73.

Bidisha Chakraborty (1), PiyabiSarkar (2), Palas Bhattacharya (3), Triparna Ghosh (4), Krishnendu Maiti (5)

(1) Junior Resident, Department of Pathology, Nil Ratan Sircar Medical College and Hospital, Kolkata, West Bengal, India.

(2) Demonstrator/Tutor, Department of Pathology, Nil Ratan Sircar Medical College and Hospital, Kolkata, West Bengal, India.

(3) Associate Professor, Department of Pathology, Nil Ratan Sircar Medical College and Hospital, Kolkata, West Bengal, India.

(4) Junior Resident, Department of Pathology, Nil Ratan Sircar Medical College and Hospital, Kolkata, West Bengal, India.

(5) Assistant Professor, Department of Urosurgery, Institute of Post Graduate Medical Education and Research (IPGMER), Kolkata, West Bengal, India.

'Financial or Other Competing Interest': None.

Submission 20-01-2019, Peer Review 24-02-2019,

Acceptance 02-03-2019, Published 11-03-2019.

Corresponding Author:

Dr. Palas Bhattacharya,

HaripalP. O, Hooghly-712403,

West Bengal, India.

E-mail: palubandhu@gmail.com

DOI: 10.14260/jemds/2019/156

Caption: Figure 1. H&E photomicrographs of different subtypes of RCCs at 400X magnification: (a) Low Grade (Grade 1) Clear Cell Renal Cell Carcinoma (b) High Grade (Grade 4) Clear Cell Renal Cell Carcinoma (c) Papillary Renal Cell Carcinoma (d) Chromophobe Renal Cell Carcinoma

Caption: Figure 2. VEGF Expression in different Subtypes of RCC at 400X Magnification: (a) Low Grade (Grade 1) CCRCC Showing 1+ VEGF Positivity (2) High Grade (Grade 4) CCRCC showing 2+ VEGF Positivity (c) PRCC Showing 2+ VEGF Positivity (d) ChRCC Showing 1+ VEGF Positivity

Caption: Figure 3. Ki-67 Expression in different Subtypes of RCC at 400X Magnification: (a) Low Grade (Grade 1) CCRCC Showing Ki-67 <15% (2) High Grade (Grade 4) CCRCC Showing Ki-67 [greater than or equal to] 15% (c) PRCC Showing Ki-67 [greater than or equal to] 15% (d) ChRCC Showing Ki-67 [greater than or equal to] 15%
Table 1. Correlation of VEGF Grade with Stage and
Histological Grade of RCC

Tumour         VEGF Grades                        Total      p-Value
Stage               0           1         2
I                   8           1         1          10      <0.00001
                  (80%)       (10%)     (10%)     (100.0%)
II                  2           8         4          14
                 (14.3%)     (57.1%)   (28.6%)    (100.0%)
III                 0          12         13         25
                  (0%)       (48.0%)   (52.0%)     (100%)
IV                  0           0         1          1
                  (0%)        (0%)     (100.0%)    (100%)

Tumour Grade

1               4 (66.7%)       2         0          6       <0.00001
                             (33.3%)    (0.0%)     (100%)
2               5 (31.3%)      11         0          16
                             (68.8%)    (0.0%)     (100%)
3               0 (0.0%)        5         7          12
                             (41.7%)   (58.3%)     (100%)
4               0 (0.0%)        2         12         14
                             (14.3%)   (85.7%)     (100%)

Table 2. Correlation of Ki-67 Labelling Index with Stage

Tumour         Ki-67 Labelling Index               Total      p- Value
Stage             <15%      [greater than or
                              equal to]15%

I              9 (90.0%)        1 (10.0%)       10 (100.0%)   <0.00001
II             6 (42.9%)        8 (57.1%)       14 (100.0%)
III            8 (32.0%)       17 (68.0%)       25 (100.0%)
IV              0 (0.0%)       1 (100.0%)       1 (100.0%)

Tumour Grade                                                  <0.00001
1              6 (100.0%)       0 (0.0%)        6 (100.0%)
2              15 (93.8%)       1 (6.3%)        16 (100.0%)
3               0 (0.0%)       12 (100.0%)      12 (100.0%)
4               0 (0.0%)       14 (100.0%)      14 (100.0%)

Table 3. Correlation of VEGF Expression With Presence of
Lymphovascular Invasion and Necrosis

Necrosis   VEGF Grades                          Total     p-Value
                0           1          2
Present         1          13         17          31
             (3.2%)      (41.9%)    (54.8%)    (100.0%)   0.0002
Absent      9 (47.4%)       8          2          19
                         (42.1%)    (10.5%)    (100.0%)

Lymphovascular Invasion

Present         1           8         13          22
             (4.5%)      (36.4%)    (59.1%)    (100.0%)   0.0083
Absent      9 (32.1%)      13      6 (21.4%)      28
                         (46.4%)               (100.0%)

Table 4. Correlation of VEGF Grade with Ki-67 Labelling Index

Ki-67               VEGF Grade
Labelling               0           1         2       Total
Index

<15%                    10         13         0         23
                     (43.5%)     (56.5%)   (0.0%)    (100.0%)
[greater than 15%       0           8        19         27
or equal to]          (0.0%)     (29.6%)   (70.4%)   (100.0%)

Ki-67
Labelling           p-Value
Index

<15%
                    <0.0001
[greater than 15%
or equal to]
COPYRIGHT 2019 Akshantala Enterprises Private Limited
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2019 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:Original Research Article
Author:Chakraborty, Bidisha; Sarkar, Piyabi; Bhattacharya, Palas; Ghosh, Triparna; Maiti, Krishnendu
Publication:Journal of Evolution of Medical and Dental Sciences
Article Type:Report
Geographic Code:9INDI
Date:Mar 11, 2019
Words:4826
Previous Article:THE ROLE OF IMMUNOHISTOCHEMISTRY IN DIAGNOSIS OF LUNG CANCER WITH CORRELATION OF SERUM TUMOUR MARKER CARCINOEMBRYONIC ANTIGEN.
Next Article:AWARENESS OF ULCERATIVE LESIONS AMONG EASTERN ODISHA POPULATION.
Topics:

Terms of use | Privacy policy | Copyright © 2020 Farlex, Inc. | Feedback | For webmasters