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. 2022 Dec 1;39(4):245-253.
doi: 10.4274/tjh.galenos.2022.2022.0046. Epub 2022 Aug 15.

Predictive Immune Markers for Disease Progression in Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

İrem Şahver İşgör  1 , Tayfur Toptaş  2 , Hüseyin Kemal Türkoz  3
Affiliations

Predictive Immune Markers for Disease Progression in Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

İrem Şahver İşgör et al. Turk J Haematol. .

Abstract
in English, Turkish

Objective: Multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM, are plasma cell neoplasms. The evolution of the treatment of MM in recent years has dramatically improved the outcome for these patients. Currently, multidisciplinary studies are being conducted to elucidate the etiopathogenesis of the disease and develop specific treatment agents and prognostic markers. The present study investigates the relationships between immunoexpression of CD138, Pan-Ras, CCL-3, DKK-1, and MUM-1 and disease progression in cases of MM and MGUS.

Materials and methods: Immunohistochemical staining for CD138, Pan-Ras, CCL-3, DKK-1, and MUM-1 were performed on bone marrow biopsy samples from 94 MM and 20 MGUS patients diagnosed between 2011 and 2018. Immunohistochemical results were examined semiquantitatively, and the associations between the immunohistochemical, clinical, and biochemical markers utilized for MM and MGUS patient staging were analyzed.

Results: Pan-Ras, DKK-1, and MUM-1 staining results were significantly higher in MM compared to MGUS (p=0.005, 0.001, and 0.001, respectively). The mean CCL-3 expression in patients with MGUS was 23.15%, while it was 18.68% in cases of MM (p=0.413). CCL-3 expression was significantly higher in high-risk MGUS cases compared to other risk groups according to the Mayo Clinic Risk Stratification for MGUS. According to the International Staging System and the Revised International Staging System, CD138 expression was higher among stage II and stage III patients than stage I patients.

Conclusion: Differences in Pan-Ras, MUM-1, DKK-1, and CCL-3 expressions between MM and MGUS suggest that these molecules may play a role in the progression of MGUS to MM. CCL-3, an immunohistochemical marker, may be predictive of MGUS progression, while CD138 is associated with more advanced stages of MM.

Amaç: Multipl myelom (MM) ve MM’nin prekürsörü olan önemi belirsiz monoklonal gamopati (MGUS), plazma hücreli neoplazilerdir. Güncel çalışmalarda bu hastalıkların etiyopatogenezini aydınlatmak, spesifik tedavi ajanları ve prognostik belirteçler geliştirmek için multidisipliner çalışmalar yürütülmektedir. Çalışmamızda MM ve MGUS’lerde CD138, Pan-Ras, CCL-3, DKK-1 ve MUM1 immünoekspresyonun hastalık evreleriyle olan ilişkisini araştırmayı hedefledik.

Gereç ve yöntemler: 2011-2018 yılları arasında tanı alan 94 MM ve 20 MGUS olgusuna ait kemik iliği biyopsilerine, CD138, Pan-Ras, CCL-3, DKK-1, MUM-1 immünohistokimyasal (İHK) boyaması yapıldı. İHK sonuçları semi kantitatif olarak değerlendirildi ve MM ve MGUS olgularının hastalık evreleriyle olan ilişkileri değerlendirildi.

Bulgular: Pan-Ras, DKK-1 ve MUM-1 immünoekspresyonu, MM’li olgularda MGUS’li olgulara göre anlamlı olarak daha yüksek saptandı (p=0,005, 0,001, ve 0,001, sırasıyla). MGUS olgularında ortalama CCL-3 immünoekspresyonu %23,15 iken, MM olgularında %18,68 idi (p=0,413). MGUS olgularında Mayo Klinik risk sınıflandırması (MCRS) modeline göre, yüksek riskli MGUS olgularında diğer risk gruplarına kıyasla CCL-3 ekspresyonu önemli ölçüde artmış olarak saptandı. CD138 ekspresyonu, ISS ve R-ISS sınıflama sistemlerine göre, evre 2 ve evre 3 hastalarda evre 1 hastalara göre artmış olarak tespit edildi.

Sonuç: MM ve MGUS olgularında Pan-Ras, MUM-1, DKK-1 ve CCL-3 ekspresyonlarındaki farklılıklar, bu belirteçlerin MGUS-MM progresyonunda önemli roller üstlendiğini göstermektedir. Kemik iliği biyopsilerinde, kolay ve pratik bir şekilde, CCL-3 immün belirteci MGUS progresyonunda prediktif; CD138 ise MM olgularında ileri evre tayininde kullanılabilir.

Keywords: CCL-3; DKK-1; MUM-1; Pan-Ras; Multiple myeloma; Monoclonal gammopathy of undetermined significance.

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Conflict of interest statement

Conflict of Interest: No conflict of interest was declared by the authors.

Figures

Figure 1
Figure 1
Expression of immunohistochemical markers in multiple myeloma: (A) MUM-1 expression in atypical plasma cells, 90%, 400x. (B) Pan-Ras expression in atypical plasma cells, 30%, 400x. (C) DKK-1 expression in atypical plasma cells, 95%, 200x. (D) CCL-3 expression in atypical plasma cells, 80%, 400x.
Figure 2
Figure 2
Expression of immunohistochemical markers in monoclonal gammopathy of undetermined significance. (A) Hematoxylin and eosin staining, 40x. (B) CD138 expression in atypical plasma cells, 6%, 40x. (C) MUM-1 expression in atypical plasma cells, 80%, 40x. (D) Pan-Ras expression in atypical plasma cells, 0%, 40x.
See this image and copyright information in PMC

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