Phosphohistone 3 (PHH3) and lactate dehydrogenase 5 (LDH5) are expressed in ductal carcinoma in situ of the breast: possible clinical implications

Martin Sillem, Sascha Baum, Stefanie Engist, Gian Kayser, Martin Werner, Sylvia Timme-Bronsert

Abstract


Purpose: Proliferation and pre-malignancy are typical features of DCIS. The expression of PHH3 as a marker for proliferation and LDH 5 as an indicator for oxygen independent energy metabolism was investigated in order to assess their potential for an improved characterisation of these lesions. Methods: Archived tissue blocks and clinical records of 130 patients with DCIS. Immunohistochemistry for PHH3, LDH5, estrogen receptor (ER), progesterone receptor (PR), human EGF receptor 2 (HER2). Silverstein nuclear grading. Chi Square test for all factors. Results: Percentage of positive patients was 69% for PHH3, 94% for LDH5, 76% for ER, 67% for PR, and 21% for HER2. Significant correlation was seen between PHH3 and LDH5 expression. No correlation could be found for any of the other comparisons. Conclusion: This is the first description of PHH3 and LDH5 in DCIS. The biological significance of PHH3 remains to be determined in a larger set of patients. LDH5 may be a useful diagnostic marker in the future. Positive HER2 receptors were considerably less frequent than previously reported.

Keywords


DCIS, PHH3, LDH5, Immunohistochemistry, clinical implications

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References


Flanagan M, Love S, Hwang ES. Status of Intraductal Therapy for Ductal Carcinoma in Situ. Curr Breast Cancer Rep, 2010. 2:75–82.

Balleine RL, Webster LR, Davis S, et al. Molecular Grading of Ductal Carcinoma In situ of the Breast. Clin Cancer Res, 2008. 14(24):8244-8252.

Sanders ME, Schuyler PA, Dupont WD, et al. The Natural History of Low-Grade Ductal Carcinoma in Situ of the Breast in Women Treated by Biopsy Only Revealed Over 30 Years of Long-Term Follow-Up. Cancer, 2005. 103(12):2481-2484.

Boughey JC, Gonzalez RJ, Bonner E, et al. Current Treatment and Clinical Trial Developments for Ductal Carcinoma In Situ of the Breast. Oncologist, 2007. 12:1276–1287.

Asjoe FT, Altintas S, Huizing MT, et al. The Value of the Van Nuys Prognostic Index in Ductal Carcinoma In Situ of the Breast: A Retrospective Analysis. Breast J, 2007. 13(4):359–367.

Bijker N, Meijnen P, Peterse JL, et al. Breast-Conserving Treatment With or Without Radiotherapy in Ductal Carcinoma-In-Situ: Ten-Year Results of European Organisation for Research and Treatment of Cancer Randomized Phase III Trial 10853—A Study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group. J Clin Oncol, 2006. 24(21):3381-3387.

Harris EER, Solin LJ. The Diagnosis and Treatment of Ductal Carcinoma In Situ of the Breast. Breast J, 2000. 6(2):78-95.

Tavassoli FA, Schnitt SJ, Hoefler H, et al. Intraductal Proliferative Lesions In: Tavassoli, F.A., Devilee, P., eds World Health Organization (WHO) Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. 1st edn., International Agency for Research on Cancer (IARC) Press, Lyon, 2000: 63-73.

Silverstein MJ. The University of Southern California/Van Nuys Prognostic Index for Ductal Carcinoma In Situ of the Breast. Am J Surg, 2003. 186(4):337-343.

Kelley L, Silverstein M, Guerra L. Analyzing the risk of recurrence after mastectomy for DCIS: a new use for the USC/Van Nuys Prognostic Index. Ann Surg Oncol, 2011. 18(2):459-562.

MacAusland SG, Hepel JT, Chong FK, et al. An Attempt to Independently Verify the Utility of the Van Nuys Prognostic Index for Ductal Carcinoma In Situ. Cancer, 2007. 110(12):2648-2653.

Altintas S, Lambein K, Huizing MT, et al. Prognostic Significance of Oncogenic Markers in Ductal Carcinoma In Situ of the Breast: A Clinicopathologic Study. Breast J, 2009. 15(2):120–132.

Joslyn SA. Ductal Carcinoma in Situ: Trends in Geographic, Temporal, and Demographic Patterns of Care and Survival. Breast J, 2006. 12(1):20–27.

Leonard GD, Swain SM. Ductal Carcinoma In Situ, Complexities and Challenges. J Natl Cancer Inst, 2004. 96(12):906-920.

Dobrescu A, Chang M, Kirtani V, et al. Study of Estrogen Receptor and Progesterone Receptor Expression in Breast Ductal Carcinoma In Situ by Immunohistochemical Staining in ER/PgR-Negative Invasive Breast Cancer. ISRN Oncology, 2011:673790.

Collins LC, Schnitt SJ. HER2 protein overexpression in estrogen receptor-positive ductal carcinoma in situ of the breast: frequency and implications for tamoxifen therapy. Mod Pathol, 2005. 18:615–620.

Boland GP, McKeown A, Chan KC, et al. Biological response to hormonal manipulation in oestrogen receptor positive ductal carcinoma in situ of the breast. Br J Cancer, 2003. 89(2):277–283.

Fisher B, Dignam J, Wolmark N, et al. Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial. Lancet, 1999. 353(9169):1993-2000.

Fisher B, Land S, Mamounas E, et al. Prevention of invasive breast cancer in women with ductal carcinoma in situ: an update of the National Surgical Adjuvant Breast and Bowel Project experience. Semin Oncol, 2001. 28(4):400-418.

Virnig BA, Tuttle TM, Shamliyan T, et al. Ductal carcinoma in situ of the breast: a systematic review of incidence, treatment, and outcomes. J Natl Cancer Inst, 2010. 102(3):170-178.

Rueschoff J, Nagelmeier I, Hofmann M, et al. Aktuelles zur ErbB2-Diagnostik beim Mammakarzinom. Pathologe, 2009. 30:147–155.

Zagouri F, Sergentanis TN, Zografos GC. Precursors and preinvasive lesions of the breast: the role of molecular prognostic markers in the diagnostic and therapeutic dilemma. World J Surg Oncol, 2007. 5: 57-67.

Yamashita H, Nishio M, Toyama T, et al. Coexistence of HER2 over-expression and p53 protein accumulation is a strong prognostic molecular marker in breast cancer. Breast Cancer Res, 2004. 6(1):24-30.

Siziopikou KP, Anderson SJ, Cobleigh MA, et al. Preliminary results of centralized HER2 testing in ductal carcinoma in situ (DCIS): NSABP B-43. Breast Cancer Res Treat, 2013. 142(2):415-421.

Borgquist S, Zhou W, Jirström K, et al. The prognostic role of HER2 expression in ductal breast carcinoma in situ (DCIS); a population-based cohort study. BMC Cancer, 2015. 11;15:468.

Bode AM, Dong Z. Inducible covalent posttranslational modification of histone H3. Sci STKE, 2005. 281:re4.

Duan Q, Chen H, Costa M, et al. Phosphorylation of H3S10 Blocks the Access of H3K9 by Specific Antibodies and Histone Methyltransferase. Implication in Regulating Chromatin Dynamica and Epigenetic Inheritance During Mitosis. J Biol Chem, 2008. 283(48):33585–33590.

Juan G, Traganos F, James WM, et al. Histone H3 Phosphorylation and Expression of Cy-clins A and B1 Measured in Individual Cells During Their Progression Through G2 and Mitosis. Cytometry, 1998. 32:71–77.

Bossard C, Jarry A, Colombeix C, et al. Phosphohistone H3 labelling for histoprognostic grading of breast adenocarcinomas and computerassisted de-termination of mitotic index. J Clin Pathol, 2006. 59:706–710.

Tapia C, Kutzner H, Mentzel T, et al. Two Mitosis-Specific Antibodies, MPM-2 and Phospho-Histone H3 (Ser28), Allow Rapid and Precise Determination of Mitotic Activity. Am J Surg Pathol, 2006. 30(1):83-89.

Skaland I, Janssen EAM, Gudlaugsson E, et al. Validating the prognostic value of proliferation measured by Phosphohistone H3 (PPH3) in invasive lymph node-negative breast cancer patients less than 71 years of age. Breast Cancer Res Treat, 2009. 114:39–45.

Skaland I, Janssen EAM, Gudlaugsson E, et al. Phosphohistone H3 expression has much stronger prognostic value than classical prognosticators in invasive lymph node-negative breast cancer patients less than 55 years of age. Mod Pathol, 2007. 20:1307-1315.

Koukourakis MI, Giatromanolaki A, Sivridis E, et al. Lactate Dehydrogenase 5 Expression in Operable Colorectal Cancer: Strong Association With Survival and Activated Vascular Endothelial Growth Factor Pathway-A Report of the Tumour Angiogenesis Research Group. J Clin Oncol, 2006. 24(26):4301-4308.

Koukourakis MI, Giatromanolaki A, Sivridis E. Lactate dehydrogenase isoenzymes 1 and 5: differential expression by neoplastic and stromal cells in non-small cell lung cancer and other epithelial malignant tumours. Tumour Biol, 2003. 24(4):199-202.

Kolev Y, Uetake H, Takagi Y, et al. Lactate Dehydrogenase-5 (LDH-5) Expression in Human Gastric Cancer: Association with Hypoxia-Inducible Factor (HIF-1a) Pathway, Angiogenic Factors Production and Poor Prognosis. Ann Surg Oncol, 2008. 15(8):2336–2344.

Balinsky D, Platz CE, Lewis JW. Isozyme Patterns of Normal, Benign, and Malignant Human Breast Tissues. Cancer Res, 1983. 43:5895-5901.

Kreienberg R, Kopp I, Albert U, et al. Ductales Carcinoma in Situ. In: Interdisziplinäre S3-Leitlinie für die Diagnostik, Therapie und Nachsorge des Mammakarzinoms. Deutsche Krebsgesellschaft e.V. (DKG) und Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG). 1st update, Zuckschwerdt, Kornwestheim, Wien, Port Washington, NY 2008. 178-181.

American Cancer Society, Cancer Facts & Figures 2012. American Cancer Society Inc., Atlanta 2012.

Weigel S, Batzler WU, Decker T, et al. First epidemiological analysis of breast cancer incidence and tumour characteristics after implementation of population-based digital mammography screening. Rofo, 2009. 181(12):1144-1150.

Tavassoli FA, Schnitt SJ, Hoefler H, et al. Tumours of the Breast: Intraductal proliferative lesions. In: Tavassoli FA, Devilee P eds. World Health Organization (WHO) Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. 1st ed. International Agency for Research on Cancer (IARC) Press, Lyon 2003: 63-73.

Rakovitch E, Franssen E, Kim J, et al. A comparison of risk perception and psychological morbidity in women with ductal carcinoma in situ and early invasive breast cancer. Breast Cancer Res Treat, 2003. 77(3):285-293.

Sagara Y, Mallory MA, Wong S, et al. Survival Benefit of Breast Surgery for Low-Grade Ductal Carcinoma In Situ: A Population-Based Cohort Study. JAMA Surg, 2015. 150(8):739-745.

Virnig BA, Tuttle TM, et al. Ductal Carcinoma In Situ of the Breast: A Systematic Review of Incidence, Treatment, and Outcomes. J Natl Cancer Inst, 2010. 102 (3): 170-178.

Curigliano G, Disalvatore D, Esposito A, et al. Risk of subsequent in situ and invasive breast cancer in human epidermal growth factor receptor 2-positive ductal carcinoma in situ. Ann Oncol, 2015. 26(4): 682-687.

Kayser G, Kassem A, Sienel W, et al. Lactate-Dehydrogenase 5 is overexpressed in non-small cell lung cancer and correlates with the expression of the transketolase-like protein 1. Diagn Pathol, 2010. 5: 22.

Zhuang L, Scolyer RA, Murali R, et al. Lactate dehydrogenase 5 expression in melanoma increases with disease progression and is associated with expression of Bcl-XL and Mcl-1, but not Bcl-2 proteins. Mod Pathol, 2010. 23: 45-53.

Kolev Y, Uetake H, Takagi Y, Sugihara K. Lactate Dehydrogenase-5 (LDH-5) Expression in Human Gastric Cancer: Association with Hypoxia-Inducible Factor (HIF-1a) Pathway, Angiogenic Factors Production and Poor Prognosis. Ann Surg Oncol, 2008. 15(8):2336–2344.

Fusco N, Runza L, Ercoli G, et al. Retained PTEN Expression Preferentially Identifies Mismatch Repair-Proficient Breast Cancers. Diagnostic Pathology, 2016. 8:191.

Gahlaut R, Arora B. Morphometric Analysis In Benign, Atypical And Invasive Breast Lesions And Its Correlation With Histological Diagnosis, Tumour Grading And Her2 Overexpression. Diagnostic Pathology, 2016. 8:118.

Traore L, Daniel C, Jaulent M-C, et al. A sustainable visual representation of available histopathological digital knowledge for breast cancer grading. Diagnostic Pathology, 2016. 2:109.




DOI: http://dx.doi.org/10.17629/www.diagnosticpathology.eu-2017-3:241



Copyright (c) 2017 Martin Sillem, Sascha Baum, Stefanie Engist, Gian Kayser, Martin Werner, Sylvia Timme-Bronsert

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