doi: 10.18081/2333-5106/015-05/232-288
M. M. Karindas
Abstract
In oncohistopathology and oncobiopathology today, various systems of measurement, appraisal, assessment and evaluation of tumor cells’ phenotypic characteristics, in vivo, are used to gather or complement data in clinical and research work. Mostly being two or three-tier scale systems based on the main histologic characteristics of cells, often including the parameters of cell differentiation nuclear size/pleomorphism, mitotic activity, tumor necrosis and proportion of solid growth and pattern of invasion, they are practically useful, but they have limited boundaries of usage in terms of interpretation and application in both clinical and research medicine, and they lack the levels of provision and contentment we critically need in research studies, case discussions, patient files, pathology reports and medical communications and transactions, and for preparing and conducting suitable and efficient oncotherapy. As we continue to use these grading systems in clinical practice and research today, we feel the vital need of a thorough, large-in-scope and all-embracing single universal grading system that we can more comprehensively and reproducibly use in clinical and research oncology and other medical fields. In this article, I present the “Karindas Grading System” (KGS), the new, wide-ranging, robust and comprehensive single cellular and tissue grading system which brings a new all-encompassing universal paradigm for observing and evaluating the phenotypic and genotypic identities of human cells, in vivo, as well as the identities of the tissues they belong to.
Keywords: Tumor grading systems; KGS Grading; Oncotherapy; Tumor regression; Tumor necrosis
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References
1. Rakha EA, El-Sayed ME, Lee AHS, Elston CW, Grainge MJ et al. Prognostic Significance of Nottingham Histologic Grade in Invasive Breast Carcinoma. JCO 2008; 26(19):3153-3158. [PubMed]
2. Gleason DF. "The Veteran's Administration Cooperative Urologic Research Group: histologic grading and clinical staging of prostatic carcinoma" in Tannenbaum M. Urologic Pathology: The Prostate. Philadelphia: Lea and Febiger 1977; 171–198.
3. Akhter M, Hossain S, Rahman QB, Molla MR. A study on histological grading of oral squamous cell carcinoma and its co-relationship with regional metastasis. J Oral Maxillofac Pathol 2011; 15(2):168–176. [PubMed]
4. American Joint Committee on Cancer. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer 2010.
5. Coindre JM. Grading of soft tissue sarcomas: review and update. Arch Pathol Lab Med 2006; 130(10):1448-53. [PubMed]
6. Doshi N, Shah Siddharth A, Patel Keyuri B, Jhabuawala Munira F. Histological Grading of Oral Cancer: A comparison of different systems and their relation to lymph node metastasis. National journal of Community Medicine 2011; 2(1):136-142. [Abstract/Full-Text]
7. Bloom HJ, Richardson WW. Histological grading and prognosis in breast cancer; A study of 1409 cases of which 359 have been followed for 15 years. British Journal of Cancer 1957; 11(3):359–77. [PubMed]
8. Genestie C, Zafrani B, Asselain B, et al. Comparison of the prognostic value of Scarff-Bloom-Richardson and Nottingham histological grades in a series of 825 cases of breast cancer: Major importance of the mitotic count as a component of both grading systems. Anticancer Research 1998; 18(1B):571–6. [PubMed]
9. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 1991; 19(5):403-10. [PubMed]
10. Mirza A Naveed A, Hayes S, et al. Assessment of Histopathological Response in Gastric and Gastro-Oesophageal Junction Adenocarcinoma following Neoadjuvant Chemotherapy: Which Scoring System to Use? ISRN Pathology 2012;1:1-8. [Abstract/Full-Text]
11. Mandard AM, F. Dalibard F Mandard JC et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer 1994; 73(11):2680–2686. [PubMed]
12. Ninomiya Y, Yanagisawa A, Kato Y, Kitagawa T, Ishihara S, Nakajima T. Histological indications of a favorable prognosis with far-advanced gastric carcinomas after preoperative chemotherapy. Journal of Cancer Research and Clinical Oncology 1999;125(12):699–706. [PubMed]
13. Becker K, Mueller JD, Schulmacher C et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer 2003; 98(7):1521–1530. [PubMed]
14. Chirieac LR, Swisher SG, Ajani JA, et al. Posttherapy pathologic stage predicts survival in patients with esophageal carcinoma receiving preoperative chemoradiation. Cancer 2005; 103(7):1347-1355. [PubMed]
15. Zhou HP, Wang X, Zhang NZ. Early apoptosis in intestinal and diffuse gastric carcinomas. World J Gastroentero 2000; 6(6):898-901. [PubMed]
16. Dhaliwal CA, Graham C, Loane J. Grading of breast cancer on needle core biopsy: does a reduction in mitotic count threshold improve agreement with grade on excised specimens? J Clin Pathol 2014; 67:1106-1108. [PubMed]
17. Xu HY, Yang YL, Guan XL, Song G, Jiang AM, Shi LJ. Expression of regulating apoptosis gene and apoptosis index in primary liver cancer. World J Gastroentero 2000; 6(5):721-724. [PubMed]
18. Archana M; Bastian, Yogesh TL, Kumaraswamy KL. Various methods available for detection of apoptotic cells- A review. Indian J Cancer 2013; 50 (3):274-283. [PubMed]
19. Pollheimer MJ, Kornprat P, Lindtner RA, et al. Tumor necrosis is a new promising prognostic factor in colorectal cancer. Hum Pathol 2010; 41(12):1749-57. [PubMed]
20. Karindas MM. The “Multicellular Origin” of Cancer and the Clonal Evolution of Oncogenesis. American Journal of BioMedicine 2014; 2(1): 1–14. [Abstract/Full-Text]
21. Santos MD, Silva C, Rocha A, Matos E, Nogueira C, Lopes C. Prognostic Value of Mandard and Dworak Tumor Regression Grading in Rectal Cancer: Study of a Single Tertiary Center. ISRN Surgery 2014:1-8. [PubMed]
22. Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 1997; 12(1):19–23. [PubMed]
23. Rödel C, Martus P, Papadoupolos T, et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 2005; 23(34):8688-8696. [PubMed]
24. Thies S, Langer R. Tumor Regression Grading of Gastrointestinal Carcinomas after Neoadjuvant Treatment. Front Oncol 2013; 3:262. [PubMed]
25. Ricci SB, Cerchiari U. Spontaneous regression of malignant tumors: Importance of the immune system and other factors (Review). Oncol Lett 2010; 1(6):941–945. [PubMed]
26. McGregor TP, Maughan TS, Sharma, RA. Pathological grading of regression following neoadjuvant chemoradiation therapy: the clinical need is now. J Clin Pathol 2012; 65(10):867-871.
27. Fareed KR, Ilyas M, Kaye PV et al. Tumour regression grade (TRG) analyses in patients with resectable gastro-oesophageal adenocarcinomas treated with platinum based neoadjuvant chemotherapy. Histopathology 2009; 55(4):399–406.
28. Armstrong MR, Douek M, Schellinger D, Patronas NJ. Regression of pituitary macroadenoma after pituitary apoplexy: CT and MR studies. J Comput Assist Tomogr 1991; 15:832-834.
29. Choudhari KA, Mclorinan GC, Byrnes DP. Spontaneous regression of a primary cerebral tumor following postoperative middle cerebral artery territory infarction. Br J Neurosurg 2001; 15:179-180.
30. van Zandijcke M, Casselman J. The vanishing pituitary adenoma. Acta Neurol Belg 1994; 94:256-258.
31. Weingarten KL, Zimmerman RD, Leeds NE. Spontaneous regression of intracerebral lymphoma. Radiology 1983; 149:721-724.
32. Yamashita Y, Kumabe T, Shimizu H, Ezura M, Tominaga T. Spontaneous regression of a primary cerebral tumor following vasospasm caused by subarachnoid hemorrhage due to rupture of an intracranial aneurysm: case report. Neurol Med Chir (Tokyo) 2004; 44(4):187-190.
33. Theissig F, Kunze KD, Haroske G, Meyer W. Histological grading of breast cancer: Interobserver, reproducibility and prognostic significance. Pathol Res Pract. 1990; 186(6):732-736.
34. Elston CW. The assessment of histological differentiation in breast cancer. Aust N Z J Surg 1984; 54(1):11-15.
35. Ivshina AV, George J, Senko O, et al. Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer. Cancer Res 2006; 66:10292-10301.
36. Rosai J, Ackerman LV. The Pathology of Tumors, Part III: Grading, Staging and Classification. CA: A Cancer Journal for Clinicians 1979; 29(2):66-77.
37. Chang RT, Kirby R, Challacombe BJ. Is there a link between BPH and prostate cancer? Practitioner 2012; 256(1750):13-16.
38. Varma T, Panchani R, Goyal A, Maskey R. A case of androgen-secreting adrenal carcinoma with non-classical congenital adrenal hyperplasia. Indian J Endocr Metab 2013; 17/S1:243-5.
39. Pinder SE, Ellis IO. The diagnosis and management of pre-invasive breast disease: Ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH) – current definitions and classification. Breast Cancer Res 2003; 5(5):254–257.
40. Giede KC, Yen TW, Chibbar R, Pierson RA. Significance of Concurrent Endometrial Cancer in Women With a Preoperative Diagnosis of Atypical Endometrial Hyperplasia. J Obstet Gynaecol Can 2008; 30(10):896–901.
41. Böcker W, Decker T, Ruhnke M, Schneider W. Ductal hyperplasia and ductal carcinoma in situ. Definition–classification–differential diagnosis. Pathologe 1997; 18(1):3-18.
42. Bostwick DG, Brawer MK. Prostatic intra-epithelial neoplasia and early invasion in prostate cancer. Cancer 1987; 59(4):788-94.
43. Bostwick DG, Qian J. High-grade prostatic intraepithelial neoplasia. Modern Pathology 2004; 17:360–379.
44. Goeman L, Joniau S, Ponette D, et al. Is low-grade prostatic intraepithelial neoplasia a risk factor for cancer? Prostate Cancer Prostatic Dis 2003; 6(4):305-10.
45. Shin HJ, Ro JY. Prostatic intraepithelial neoplasia: a potential precursor lesion of prostatic adenocarcinoma. Yonsei Med J 1995; 36(3):215-31.
46. Mostofi FK, Sesterhenn IA, Davis CJ Jr. Prostatic intraepithelial neoplasia (PIN): morphological clinical significance. Prostate Suppl 1992; 4:71-77.
47. McNeal JE, Bostwick DG. Intraductal dysplasia: a premalignant lesion of the prostate. Hum Pathol 1986; 17(1):64-67.
48. Algaba F, Trias I. Diagnostic limits in precursor lesions of prostatic cancer. Eur Urol 1996; 30(2):212-21.
49. Bostwick DG. Prospective origins of prostate carcinoma. Prostatic intraepithelial neoplasia and atypical adenomatous hyperplasia. Cancer. 1996; 78(2):330-6.
50. Helpap BG, Bostwick DG, Montironi R. The significance of atypical adenomatous hyperplasia and prostatic intraepithelial neoplasia for the development of prostate carcinoma. An update. Virchows Arch 1995; 426(5):425-34.
51. Montironi R, Mazzucchelli R, Lopez-Beltran A, Cheng L, Scarpelli M. Mechanisms of disease: high-grade prostatic intraepithelial neoplasia and other proposed preneoplastic lesions in the prostate. Nat Clin Pract Urol 2007; 4(6):321-32.
52. Epstein JI. Precursor lesions to prostatic adenocarcinoma. Virchows Arch 2009; 454(1):1-16.
53. Chrisofos M, Papatsoris AG, Lazaris A, Deliveliotis C. Precursor lesions of prostate cancer. Crit Rev Clin Lab Sci 2007; 44(3):243-70.
54. Helpap B, Riede C. Nucleolar and AgNOR-analysis of prostatic intraepithelial neoplasia (PIN), atypical adenomatous hyperplasia (AAH) and prostatic carcinoma. Pathol Res Pract 1995; 191(5):381-90.
55. Rekhi B, Jaswal TS, Arora B. Premalignant lesions of prostate and their association with nodular hyperplasia and carcinoma prostate. Indian J Cancer 2004; 41(2):60-5.
56. Bostwick DG. Premalignant lesions of the prostate. Semin Diagn Pathol 1988; 5(3):240-53.
57. van de Vijver MJ. Ductal carcinoma in situ of the breast: histological classification and genetic alterations. Recent Results Cancer Res. 1998; 152:123-34.
58. Galimberti V, Monti S, Mastropasqua MG. DCIS and LCIS are confusing and outdated terms. They should be abandoned in favor of ductal intraepithelial neoplasia (DIN) and lobular intraepithelial neoplasia (LIN). Breast 2013; 22(4):431-5.
59. Bratthauer GL, Tavassoli FA. Lobular intraepithelial neoplasia: previously unexplored aspects assessed in 775 cases and their clinical implications. Virchows Arch 2002; 440(2):134-8.
60. Tavassoli FA. Ductal carcinoma in situ: introduction of the concept of ductal intraepithelial neoplasia. Mod Pathol. 1998; 11(2):140-54.
61. Algaba F, Epstein JI, Fabus G, Helpap B, Nagle RB, Polito M. Working standards in prostatic intraepithelial neoplasia and atypical adenomatous hyperplasia. Pathol Res Pract 1995; 191(9):836-7.
62. Epstein JI. An update of the Gleason grading system. J Urol 2010; 183:433-40.
63. Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL. Update on the Gleason grading system for prostate cancer: results of an international consensus conference of urologic pathologists. Adv Anat Pathol 2006; 13(1):57-9.
64. Billis A, Guimaraes MS, Freitas LL, Meirelles L, Magna LA, Ferreira U. The impact of the 2005 international society of urological pathology consensus conference on standard Gleason grading of prostatic carcinoma in needle biopsies. J Urol 2008; 180(2):548-52; discussion 552-3.
65. Gottipati S, Warncke J, Vollmer R, Humphrey PA. Usual and unusual histologic patterns of high Gleason score 8 to 10 adenocarcinoma of the prostate in needle biopsy tissue. Am J Surg Pathol 2012; 36(6):900-7.
66. San Francisco IF, DeWolf WC, Rosen S, Upton M, Olumi AF. Extended prostate needle biopsy improves concordance of Gleason grading between prostate needle biopsy and radical prostatectomy. J Urol 2003; 169(1):136-40.
67. Djavan B, Kadesky K, Klopukh B, Marberger M, Roehrborn CG. Gleason scores from prostate biopsies obtained with 18-gauge biopsy needles poorly predict Gleason scores of radical prostatectomy specimens. Eur Urol 1998; 33(3):261-70.
68. Gleason DF. Histologic grading of prostate cancer: a perspective. Hum Pathol 1992; 23:273-279.
69. Cheng L, Shan A, Cheville JC, O-an J, Bostwick DG. Atypical Adenomatous Hyperplasia of the Prostate: A Premalignant Lesion? Cancer Research 1998; 58:389-91.
70. Montironi R, Mazzucchelli R, Algaba F, Lopez-Beltran A. Morphological identification of the patterns of prostatic intraepithelial neoplasia and their importance. J Clin Pathol 2000; 53:655-665.
71. Srigley JR. Benign mimickers of prostatic adenocarcinoma. Modern Pathology 2004; 17:328–48.
72. Armah HB, Parwani AV. Atypical adenomatous hyperplasia (adenosis) of the prostate: a case report with review of the literature. Diagn Pathol 2008; 3:34.
73. Helpap B, Bonkhoff H, Cockett A, Montironi R, Troncoso P, Waters D, Bostwick D. Relationship between atypical adenomatous hyperplasia (AAH), prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma. Pathologica 1997; 89(3):288-300.
74. Helpap B. Cell Kinetic Studies on Prostatic Intraepithelial Neoplasia (PIN) and Atypical Adenomatous Hyperplasia (AAH) of the Prostate. Pathol Res Pract 1995;191(9):904–907.
75. Helpap B, Riede C. Nucleolar and AgNOR-analysis of prostatic intraepithelial neoplasia (PIN), atypical adenomatous hyperplasia (AAH) and prostatic carcinoma. Pathol Res Pract. 1995; 191(5):381-90.
76. Plaks V, Koopman CD, Werb Z. Circulating Tumor Cells. Science 2013; 341(6151):1186-8.
77. Vang R, Shih IM, Kurman RJ. OVARIAN LOW-GRADE AND HIGH-GRADE SEROUS CARCINOMA: Pathogenesis, Clinicopathologic and Molecular Biologic Features, and Diagnostic Problems. Adv Anat Pathol 2009; 16(5):267–282.
78. Gilks CB, Ionescu DN, Kalloger SE, et al. Tumor cell type can be reproducibly diagnosed and is of independent prognostic significance in patients with maximally debulked ovarian carcinoma. Hum Pathol 2008; 39(8):1239-51.
79. Seidman JD, Horkayne-Szakaly I, Cosin JA, et al. Testing of two binary grading systems for FIGO stage III serous carcinoma of the ovary and peritoneum. Gynecol Oncol 2006; 103(2):703-8.
80. Malpica A, Deavers MT, Lu K, Bodurka DC, Atkinson EN, Gershenson DM, Silva EG. Grading ovarian serous carcinoma using a two-tier system. Am J Surg Pathol 2004; 28(4):496-504.
81. Silverberg SG. Histopathologic grading of ovarian carcinoma: a review and proposal. Int J Gynecol Pathol 2000; 19:7–15.
82. Allred DC, Wu Y, Mao S, Nagtegaal ID. Ductal carcinoma in situ and the emergence of diversity during Breast Cancer Evolution. Clin Cancer Res 2008; 14:370-78.
83. Holczbauer A, Factor VM, Andersen JB, et al. Modeling Pathogenesis of Primary Liver Cancer in Lineage-Specific Mouse Cell Types. Gastroenterology 2013; 145(1):221–231.
84. Ayhan A, Kurman RJ, Vang R, Logani S, Seidman JD, Shih IM. Defining the cut-point between low- and high-grade ovarian serous carcinomas: A clinicopathologic and molecular genetic analysis. Am J Surg Pathol 2009; 33(8):1220–1224.
85. McCluggage WG. Morphological subtypes of ovarian carcinoma: a review with emphasis on new developments and pathogenesis. Pathology 2011; 43(5):420-32.
86. Dehari R, Kurman RJ, Logani S, Shih IM. The development of high-grade serous carcinoma from atypical proliferative (borderline) serous tumors and low-grade micropapillary serous carcinoma: a morphologic and molecular genetic analysis. Am J Surg Pathol 2007; 31(7):1007-12.
87. Cheung WK, Nguyen DX. Lineage factors and differentiation states in lung cancer progression. Oncogene 2015; Epub 2015 Mar 30. PMID: 25823023.
88. Shimizu Y, Kamoi S, Amada S, Akiyama F, Silverberg SG. Toward the development of a universal grading system for ovarian epithelial carcinoma: testing of a proposed system in a series of 461 patients with uniform treatment and follow-up. Cancer 1998; 82(5):893-901.
89. Hsu CY, Kurman RJ, Vang R, et al. Nuclear size distinguishes low- from high-grade ovarian serous carcinoma and predicts outcome. Hum Pathol 2005; 36:1049–54.
90. Lipponen PK, Eskelinen MJ, Kiviranta J, Pesonen E. Prognosis of transitional cell bladder cancer: a multivariate prognostic score for improved prediction. J Urol 1991; 146(6):1535-40.
91. Lipponen PK, Eskelinen MJ, Jauhiainen K, Harju E, Terho R, Haapasalo H. Grading of superficial bladder cancer by quantitative mitotic frequency analysis. J Urol 1993; 149(1):36-41.
92. Lipponen PK, Eskelinen MJ, Jauhiainen K, Harju E, Terho R, Haapasalo H. Independent clinical, histological and quantitative prognostic factors in transitional-cell bladder tumours, with special reference to mitotic frequency. Int J Cancer 1992; 51(3):396-403.
93. Parham DM. Mitotic activity and histological grading of breast cancer. Pathol Annu 1995; 30( Pt 1):189-207.
94. Meyer JS, Alvarez C, Milikowski C, et al. Breast carcinoma malignancy grading by Bloom-Richardson system vs proliferation index: reproducibility of grade and advantages of proliferation index. Mod Pathol 2005; 18(8):1067–1078.
95. Robbins P, Pinder S, de Klerk N, et al. Histological grading of breast carcinomas: a study of interobserver agreement. Hum Patho 1995 26(8):873–879.
96. Clayton F. Pathologic correlates of survival in 378 lymph node-negative infiltrating ductal breast carcinomas. Mitotic count is the best single predictor. Cancer 1991; 68(6):1309–1317.
97. Beresford MJ, Wilson GD, Makris A. Measuring proliferation in breast cancer: practicalities and applications. Breast Cancer Res 2006; 8(6):216.
98. Longacre TA, Ennis M, Quenneville LA, et al. Interobserver agreement and reproducibility in classification of invasive breast carcinoma: an NCI breast cancer family registry study. Mod Pathol 2006; 19(2):195–207.
99. Delahunt B, McKenney JK, Lohse CM, Leibovich BC, Thompson RH, Boorjian SA, Cheville JC. A novel grading system for clear cell renal cell carcinoma incorporating tumor necrosis. Am J Surg Pathol 2013;37(3):311-22.
100. Picci P, Böhling T, Bacci G, et al. Chemotherapy-induced tumor necrosis as a prognostic factor in localized Ewing's sarcoma of the extremities. JCO 1997; 15(4):1553-1559.
101. Shim B, Jung JH, Cho HM, Kim HJ, Hong JH, Kim SW. Neoadjuvant treatment response as a tumor necrosis grade for patients with rectal cancer. J Clin Oncol 31, 2013 (suppl; abstr e14563).
102. Lax SF, Kurman RJ, Pizer ES, Wu L, Ronnett BM. A binary architectural grading system for uterine endometrial endometrioid carcinoma has superior reproducibility compared with FIGO grading and identifies subsets of advance-stage tumors with favorable and unfavorable prognosis. Am J Surg Pathol 2000; 24(9):1201-8.
103. Scholten AN, Smit VT, Beerman H, van Putten WL, Creutzberg CL. Prognostic significance and interobserver variability of histologic grading systems for endometrial carcinoma. Cancer 2004; 100(4):764-72.
104. Alkushi A, Abdul-Rahman ZH, Lim P, et al. Description of a novel system for grading of endometrial carcinoma and comparison with existing grading systems. Am J Surg Pathol 2005; 29(3):295-304.
105. Zaino RJ. FIGO staging of endometrial adenocarcinoma: a critical review and proposal. Int J Gynecol Pathol 2009; 28(1):1-9.
106. Lewin SN. Revised FIGO staging system for endometrial cancer. Clin Obstet Gynecol 2011; 54(2):215-8.
107. Garg G, Shah JP, Liu JR, et al. Validation of tumor size as staging variable in the revised International Federation of Gynecology and Obstetrics stage I leiomyosarcoma: a population-based study. Int J Gynecol Cancer 2010; 20(7):1201-6.
108. Shen K, Peng P, Wu M. Clinical significance of the revised international federation of gynecology and obstetrics staging system 2009. Zhonghua Fu Chan Ke Za Zhi 2010; 45(10):721-4.
109. Delahunt B. Advances and controversies in grading and staging of renal cell carcinoma. Mod Pathol 2009; 22 Suppl 2:S24-36.
110. Novara G, Martignoni G, Artibani W, Ficarra V. Grading systems in renal cell carcinoma. J Urol 2007; 177(2):430-6.
111. Kapucuoglu N, Bulbul D, Tulunay G, Temel MA. Reproducibility of grading systems for endometrial endometrioid carcinoma and their relation with pathologic prognostic parameters. Int J Gynecol Cancer 2008; 18(4):790-6.
112. Sagae S, Saito T, Satoh M, et al. The reproducibility of a binary tumor grading system for uterine endometrial endometrioid carcinoma, compared with FIGO system and nuclear grading. Oncology 2004; 67(5-6):344-50.
113. Gilks CB, Ionescu DN, Kalloger SE, et al. Tumor cell type can be reproducibly diagnosed and is of independent prognostic significance in patients with maximally debulked ovarian carcinoma. Hum Pathol 2008; 39(8):1239-51.
114. Finley DS, Shuch B, Said JW, et al. The chromophobe tumor grading system is the preferred grading scheme for chromophobe renal cell carcinoma. J Urol 2011; 186(6):2168-74.
115. Malpica A, Deavers MT, Lu K, et al. Grading ovarian serous carcinoma using a two-tier system. Am J Surg Pathol 2004; 28(4):496-504.
116. Malpica A, Deavers MT, Tornos C, et al. Interobserver and intraobserver variability of a two-tier system for grading ovarian serous carcinoma. Am J Surg Pathol 2007; 31(8):1168-74.
117. Bodurka DC, Deavers MT, Tian C, et al. Reclassification of serous ovarian carcinoma by a 2-tier system: a Gynecologic Oncology Group Study. Cancer 2012; 118(12):3087-94.
118. Paner GP, Amin MB, Alvarado-Cabrero I, et al. A novel tumor grading scheme for chromophobe renal cell carcinoma: prognostic utility and comparison with Fuhrman nuclear grade. Am J Surg Pathol 2010; 34(9):1233-40.
119. Ueno H, Kajiwara Y, Shimazaki H, et al. New criteria for histologic grading of colorectal cancer. Am J Surg Pathol 2012; 36(2):193-201.
120. Ueno H, Hase K, Hashiguchi Y, et al. Site-specific tumor grading system in colorectal cancer: multicenter pathologic review of the value of quantifying poorly differentiated clusters. Am J Surg Pathol 2014; 38(2):197-204.
121. Ueno H, Mochizuki H, Hashiguchi Y, et al. Histological grading of colorectal cancer: a simple and objective method. Ann Surg 2008; 247(5):811-8.
122. Takeuchi K, Kuwano H, Tsuzuki Y, Ando T, Sekihara M, Hara T, Asao T. Clinicopathological characteristics of poorly differentiated adenocarcinoma of the colon and rectum. Hepatogastroenterology 2004; 51(60):1698-702.
123. Ramanathan RC, A'Hern R, Fisher C, Thomas JM. Modified staging system for extremity soft tissue sarcomas. Ann Surg Oncol. 1999; 6(1):57-69.
124. Kim JW, Shin MK, Kim BC. Clinicopathologic impacts of poorly differentiated cluster-based grading system in colorectal carcinoma. J Korean Med Sci 2015; 30(1):16-23.
125. Rosty C, Williamson EJ, Clendenning M, et al. Should the grading of colorectal adenocarcinoma include microsatellite instability status? Hum Pathol 2014; 45(10):2077-84.
126. Barresi V, Reggiani Bonetti L, Branca G, Di Gregorio C, Ponz de Leon M, Tuccari G. Colorectal carcinoma grading by quantifying poorly differentiated cell clusters is more reproducible and provides more robust prognostic information than conventional grading. Virchows Arch 2012; 461(6):621-8.
127. Barresi V, Bonetti LR, Ieni A, Branca G, Baron L, Tuccari G. Histologic grading based on counting poorly differentiated clusters in preoperative biopsy predicts nodal involvement and pTNM stage in colorectal cancer patients. Hum Pathol 2014; 45(2):268-75.
128. Taborda AG, Prolla JC. Fatores alimentares envolvidos no desenvolvimento de metaplasia intestinal em dispépticos funcionais. Arq Gastroenterol 2012; 49(3).
129. Genta RM, Rugge M. Review article: pre-neoplastic states of the gastric mucosa – a practical approach for the perplexed clinician. Aliment Pharmacol Ther 2001; 15(Suppl 1):43-50.
130. Saikawa Y, Fukuda K, Takahashi T, Nakamura R, Takeuchi H, Kitagawa Y. Gastric carcinogenesis and the cancer stem cell hypothesis. Gastric Cancer 2010; 13:11-24.
131. Shah MA, Ajani JA. Gastric cancer an enigmatic and heterogeneous disease. JAMA 2010; 303:1753-4.
132. Bratthauer GL, Tavassoli FA. Assessment of lesions coexisting with various grades of ductal intraepithelial neoplasia of the breast. Virchows Arch 2004; 444(4):340-344.
133. Aaltomaa S, Lipponen P, Eskelinen M et al. Mitotic indexes as prognostic predictors in female breast cancer. J Cancer Res Clin Oncol 1992; 118(1):75-81.
134. Greaves M, Maley CC. CLONAL EVOLUTION IN CANCER. Nature 2012; 481(7381):306–313.
135. Guan H, Semaan A, Bandyopadhyay S, et al. Prognosis and reproducibility of new and existing binary grading systems for endometrial carcinoma compared to FIGO grading in hysterectomy specimens. Int J Gynecol Cancer 2011; 21(4):654-60.
