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BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Breast Cancer | Research

Prognostic value of tumor necrosis based on the evaluation of frequency in invasive breast cancer

Authors: Jianhua Chen, Zhijun Li, Zhonghua Han, Deyong Kang, Jianli Ma, Yu Yi, Fangmeng Fu, Wenhui Guo, Liqin Zheng, Gangqin Xi, Jiajia He, Lida Qiu, Lianhuang Li, Qingyuan Zhang, Chuan Wang, Jianxin Chen

Published in: BMC Cancer | Issue 1/2023

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Abstract

Background

Tumor necrosis (TN) was associated with poor prognosis. However, the traditional classification of TN ignored spatial intratumor heterogeneity, which may be associated with important prognosis. The purpose of this study was to propose a new method to reveal the hidden prognostic value of spatial heterogeneity of TN in invasive breast cancer (IBC).

Methods

Multiphoton microscopy (MPM) was used to obtain multiphoton images from 471 patients. According to the relative spatial positions of TN, tumor cells, collagen fibers and myoepithelium, four spatial heterogeneities of TN (TN1-4) were defined. Based on the frequency of individual TN, TN-score was obtained to investigate the prognostic value of TN.

Results

Patients with high-risk TN had worse 5-year disease-free survival (DFS) than patients with no necrosis (32.5% vs. 64.7%; P < 0.0001 in training set; 45.8% vs. 70.8%; P = 0.017 in validation set), while patients with low-risk TN had a 5-year DFS comparable to patients with no necrosis (60.0% vs. 64.7%; P = 0.497 in training set; 59.8% vs. 70.8%; P = 0.121 in validation set). Furthermore, high-risk TN “up-staged” the patients with IBC. Patients with high-risk TN and stage I tumors had a 5-year DFS comparable to patients with stage II tumors (55.6% vs. 62.0%; P = 0.565 in training set; 62.5% vs. 66.3%; P = 0.856 in validation set), as well as patients with high-risk TN and stage II tumors had a 5-year DFS comparable to patients with stage III tumors (33.3% vs. 24.6%; P = 0.271 in training set; 44.4% vs. 39.3%; P = 0.519 in validation set).

Conclusions

TN-score was an independent prognostic factor for 5-year DFS. Only high-risk TN was associated with poor prognosis. High-risk TN “up-staged” the patients with IBC. Incorporating TN-score into staging category could improve its performance to stratify patients.
Appendix
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Literature
1.
Sengupta S, Lohse CM, Leibovich BC, Frank I, Thompson RH, Webster WS, et al. Histologic coagulative tumor necrosis as a prognostic indicator of renal cell carcinoma aggressiveness. Cancer. 2005;104(3):511–20.PubMedCrossRef
2.
Langner C, Hutterer G, Chromecki T, Leibl S, Rehak P, Zigeuner R. Tumor necrosis as prognostic indicator in transitional cell carcinoma of the upper urinary tract. J Urol. 2006;176(3):910–3 (discussion 913-4).PubMedCrossRef
3.
Kuroe T, Watanabe R, Kojima M, Morisue R, Sugano M, Kuwata T, et al. Evaluation of the morphological features and unfavorable prognostic impact of dirty necrosis in renal cell carcinoma. J Cancer Res Clin Oncol. 2021;147(4):1089–100.PubMedCrossRef
4.
Hiraoka N, Ino Y, Sekine S, Tsuda H, Shimada K, Kosuge T, et al. Tumour necrosis is a postoperative prognostic marker for pancreatic cancer patients with a high interobserver reproducibility in histological evaluation. Br J Cancer. 2010;103(7):1057–65.PubMedPubMedCentralCrossRef
5.
Edwards JG, Swinson DE, Jones JL, Muller S, Waller DA, O’Byrne KJ. Tumor necrosis correlates with angiogenesis and is a predictor of poor prognosis in malignant mesothelioma. Chest. 2003;124(5):1916–23.PubMedCrossRef
6.
Wei T, Zhang XF, Bagante F, Ratti F, Marques HP, Silva S, et al. Tumor necrosis impacts prognosis of patients undergoing curative-intent hepatocellular carcinoma. Ann Surg Oncol. 2021;28(2):797–805.PubMedCrossRef
7.
Swinson DE, Jones JL, Richardson D, Cox G, Edwards JG, O’Byrne KJ. Tumour necrosis is an independent prognostic marker in non-small cell lung cancer: correlation with biological variables. Lung Cancer. 2002;37(3):235–40.PubMedCrossRef
8.
Richards CH, Roxburgh CS, Anderson JH, McKee RF, Foulis AK, Horgan PG, et al. Prognostic value of tumour necrosis and host inflammatory responses in colorectal cancer. Br J Surg. 2012;99(2):287–94.PubMedCrossRef
9.
Pollheimer MJ, Kornprat P, Lindtner RA, Harbaum L, Schlemmer A, Rehak P, et al. Tumor necrosis is a new promising prognostic factor in colorectal cancer. Hum Pathol. 2010;41(12):1749–57.PubMedCrossRef
10.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.PubMedCrossRef
11.
Leek RD, Landers RJ, Harris AL, Lewis CE. Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast. Br J Cancer. 1999;79(5–6):991–5.PubMedPubMedCentralCrossRef
12.
Dietzel M, Baltzer PA, Vag T, Herzog A, Gajda M, Camara O, et al. The necrosis sign in magnetic resonance-mammography: diagnostic accuracy in 1,084 histologically verified breast lesions. Breast J. 2010;16(6):603–8.PubMedCrossRef
13.
Gilchrist KW, Gray R, Fowble B, Tormey DC, Taylor SG. Tumor necrosis is a prognostic predictor for early recurrence and death in lymph node-positive breast cancer: a 10-year follow-up study of 728 Eastern cooperative oncology group patients. J Clin Oncol. 1993;11(10):1929–35.PubMedCrossRef
14.
Lee AH, Gillett CE, Ryder K, Fentiman IS, Miles DW, Millis RR. Different patterns of inflammation and prognosis in invasive carcinoma of the breast. Histopathology. 2006;48(6):692–701.PubMedCrossRef
15.
Fisher ER, Palekar AS, Gregorio RM, Redmond C, Fisher B. Pathological findings from the national surgical adjuvant breast project (Protocol No. 4). IV. Significance of tumor necrosis. Hum Pathol. 1978;9(5):523–30.PubMedCrossRef
16.
Vincent-Salomon A, Carton M, Zafrani B, Fréneaux P, Nicolas A, Massemin B, et al. Long term outcome of small size invasive breast carcinomas independent from angiogenesis in a series of 685 cases. Cancer. 2001;92(2):249–56.PubMedCrossRef
17.
Maiorano E, Regan MM, Viale G, Mastropasqua MG, Colleoni M, Castiglione-Gertsch M, et al. Prognostic and predictive impact of central necrosis and fibrosis in early breast cancer: results from two International breast cancer study group randomized trials of chemoendocrine adjuvant therapy. Breast Cancer Res Treat. 2010;121(1):211–8.PubMedCrossRef
18.
Kato T, Kameoka S, Kimura T, Nishikawa T, Kobayashi M. The combination of angiogenesis and blood vessel invasion as a prognostic indicator in primary breast cancer. Br J Cancer. 2003;88(12):1900–8.PubMedPubMedCentralCrossRef
19.
Richards CH, Mohammed Z, Qayyum T, Horgan PG, McMillan DC. The prognostic value of histological tumor necrosis in solid organ malignant disease: a systematic review. Future Oncol. 2011;7(10):1223–35.PubMedCrossRef
20.
Kato T, Kimura T, Miyakawa R, Fujii A, Yamamoto K, Kameoka S, et al. Clinicopathologic study associated with long-term survival in Japanese patients with node-negative breast cancer. Br J Cancer. 2000;82(2):404–11.PubMedPubMedCentralCrossRef
21.
Urru SAM, Gallus S, Bosetti C, Moi T, Medda R, Sollai E, et al. Clinical and pathological factors influencing survival in a large cohort of triple-negative breast cancer patients. BMC Cancer. 2018;18(1):56.PubMedPubMedCentralCrossRef
22.
Klatte T, Said JW, de Martino M, Fujii A, Yamamoto K, Kameoka S, et al. Presence of tumor necrosis is not a significant predictor of survival in clear cell renal cell carcinoma: higher prognostic accuracy of extent based rather than presence/absence classification. J Urol. 2009;181(4):1558–64 (discussion 1563-64).PubMedCrossRef
23.
24.
Thomas G, van Voskuilen J, Gerritsen HC, Sterenborg HJ. Advances and challenges in label-free nonlinear optical imaging using two-photon excitation fluorescence and second harmonic generation for cancer research. J Photochem Photobiol B Biol. 2014;141:128–38.CrossRef
25.
Zipfel WR, Williams RM, Christie R, Nikitin AY, Hyman BT, Webb WW. Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. Proc Natl Acad Sci USA. 2003;100(12):7075–80.PubMedPubMedCentralCrossRef
26.
Borile G, Sandrin D, Filippi A, Anderson KI, Romanato F. Label-free multiphoton microscopy: much more than fancy images. Int J Mol Sci. 2021;22(5):2657.PubMedPubMedCentralCrossRef
27.
Campagnola PJ, Loew LM. Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms. Nat Biotechnol. 2003;21(11):1356–60.PubMedCrossRef
28.
Brown E, McKee T, diTomaso E, Pluen A, Seed B, Boucher Y, et al. Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation. Nat Med. 2003;9(6):796–800.PubMedCrossRef
29.
Xi G, Guo W, Kang D, Ma J, Fu F, Qiu L, et al. Large-scale tumor-associated collagen signatures identify high-risk breast cancer patients. Theranostics. 2021;11(7):3229–43.PubMedPubMedCentralCrossRef
30.
He J, Fu F, Wang W, Xi G, Guo W, Zheng L, et al. Prognostic value of tumour-infiltrating lymphocytes based on the evaluation of frequency in patients with oestrogen receptor-positive breast cancer. Eur J Cancer. 2021;154:217–26.PubMedCrossRef
31.
Cronin M, Sangli C, Liu ML, Mylan P, Dutta D, Nguyen A, et al. Analytical validation of the Oncotype DX genomic diagnostic test for recurrence prognosis and therapeutic response prediction in node-negative, estrogen receptor-positive breast cancer. Clin Chem. 2007;53(6):1084–91.PubMedCrossRef
32.
Dowsett M, Cuzick J, Wale C, Forbes J, Mallon EA, Salter J, et al. Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study. J Clin Oncol. 2010;28(11):1829–34.PubMedCrossRef
33.
Rakovitch E, Nofech-Mozes S, Hanna W, Baehner FL, Saskin R, Butler SM, et al. A population-based validation study of the DCIS Score predicting recurrence risk in individuals treated by breast-conserving surgery alone. Breast Cancer Res Treat. 2015;152(2):389–98.PubMedPubMedCentralCrossRef
34.
Cardoso F, Van’t Veer L, Rutgers E, Loi S, Mook S, Piccart-Gebhart MJ. Clinical application of the 70-gene profile: the MINDACT trial. J Clin Oncol. 2008;26(5):729–35.PubMedCrossRef
35.
Dubsky P, Brase JC, Jakesz R, Rudas M, Singer CF, Greil R, et al. The EndoPredict score provides prognostic information on late distant metastases in ER+/HER2- breast cancer patients. Br J Cancer. 2013;109(12):2959–64.PubMedPubMedCentralCrossRef
36.
Ohnstad HO, Borgen E, Falk RS, Lien TG, Aaserud M, Sveli MAT, et al. Prognostic value of PAM50 and risk of recurrence score in patients with early-stage breast cancer with long-term follow-up. Breast Cancer Res. 2017;19(1):120.PubMedPubMedCentralCrossRef
37.
Tavernar D, Battistello E, Dheill E, Petruzzella AS, Mina M, Sordet-Dessimoz J, et al. Nongenetic evolution drives lung adenocarcinoma spatial heterogeneity and progression. Cancer Discov. 2021;11(6):1490–507.CrossRef
38.
Sántha P, Lenggenhager D, Finstadsveen A, Dorg L, Tøndel K, Amrutkar M, et al. Morphological heterogeneity in pancreatic cancer reflects structural and functional divergence. Cancers (Basel). 2021;13(4):895.PubMedCrossRef
39.
40.
Bera K, Kiepas A, Zhang Y, Sun SX, Konstantopoulos K. The interplay between physical cues and mechanosensitive ion channels in cancer metastasis. Front Cell Dev Biol. 2022;10:954099.PubMedPubMedCentralCrossRef
41.
Conklin MW, Eickhoff JC, Riching KM, Pehlke CA, Eliceiri KW, Provenzano PP, et al. Aligned collagen is a prognostic signature for survival in human breast carcinoma. Am J Pathol. 2011;178(3):1221–32.PubMedPubMedCentralCrossRef
42.
Provenzano PP, Eliceiri KW, Campbell JM, Inman DR, White JG, Keely PJ. Collagen reorganization at the tumor-stromal interface facilitates local invasion. BMC Med. 2006;4(1):38.PubMedPubMedCentralCrossRef
43.
Conklin MW, Gangnon RE, Sprague BL, Van Gemert L, Hampton JM, Eliceiri KW, et al. Collagen alignment as a predictor of recurrence after ductal carcinoma in situ. Cancer Epidemiol Biomarkers Prev. 2018;27(2):138–45.PubMedCrossRef
44.
Skala MC, Riching KM, Gendron-Fitzpatrick A, Eickhoff J, Eliceiri KW, White JG, et al. In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia. Proc Natl Acad Sci U S A. 2007;104(49):19494–9.PubMedPubMedCentralCrossRef
45.
Quinn KP, Sullivan KE, Liu Z, Ballard Z, Siokatas C, Georgakoudi I, et al. Optical metrics of the extracellular matrix predict compositional and mechanical changes after myocardial infarction. Sci Rep. 2016;6:35823.PubMedPubMedCentralCrossRef
46.
König K, Breunig HG, Batista A, Schindele A, Zieger M, Kaatz M. Translation of two-photon microscopy to the clinic: multimodal multiphoton CARS tomography of in vivo human skin. J Biomed Opt. 2020;25(1):1–12.PubMedCrossRef
47.
Garofalakis A, Kruglik SG, Mansuryan T, Gillibert A, Thiberville L, Louradour F, et al. Characterization of a multicore fiber image guide for nonlinear endoscopic imaging using two-photon fluorescence and second-harmonic generation. J Biomed Opt. 2019;24(10):1–12.PubMedCrossRef
48.
Tandon I, Quinn KP, Balachandran K. Label-free multiphoton microscopy for the detection and monitoring of calcific aortic valve disease. Front Cardiovasc Med. 2021;8:688513.PubMedPubMedCentralCrossRef
49.
Konig K, Ehlers A, Riemann I, Schenkl S, Bückle R, Kaatz M. Clinical two-photon microendoscopy. Microsc Res Tech. 2007;70(5):398–402.PubMedCrossRef
50.
Sun Y, You S, Tu H, Spillman DR Jr, Chaney EJ, Marjanovic M, et al. Intraoperative visualization of the tumor microenvironment and quantification of extracellular vesicles by label-free nonlinear imaging. Sci Adv. 2018;4(12):eaau5603.PubMedPubMedCentralCrossRef
51.
Huck V, Gorzelanny C, Thomas K, Getova V, Niemeyer V, Zens K, et al. From morphology to biochemical state - intravital multiphoton fluorescence lifetime imaging of inflamed human skin. Sci Rep. 2016;6:22789.PubMedPubMedCentralCrossRef
Metadata
Title
Prognostic value of tumor necrosis based on the evaluation of frequency in invasive breast cancer
Authors
Jianhua Chen
Zhijun Li
Zhonghua Han
Deyong Kang
Jianli Ma
Yu Yi
Fangmeng Fu
Wenhui Guo
Liqin Zheng
Gangqin Xi
Jiajia He
Lida Qiu
Lianhuang Li
Qingyuan Zhang
Chuan Wang
Jianxin Chen
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-10943-x

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