The relationship between different basal cell carcinoma subtypes and Neutrophilto Lymphocyte Ratio, Platelet to Lymphocyte Ratio, and Pan- Immune- Inflammation Value


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Turan I. İ., Akpınar Ö. F., Kozanoğlu E.

12th Balkan Society of Plastic Reconstructive and Aesthetic Surgery Congress, Konya, Türkiye, 14 - 16 Eylül 2023, ss.235-236

  • Yayın Türü: Bildiri / Tam Metin Bildiri
  • Basıldığı Şehir: Konya
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.235-236
  • İstanbul Üniversitesi Adresli: Evet

Özet

The Relationship Between Different Basal Cell Carcinoma Subtypes and Neutrophil to Lymphocyte Ratio, Platelet to Lymphocyte Ratio, and Pan-Immune-Inflammation Value

 

 

Işıl İrem TURAN1 Ömer Faruk AKPINAR1, Erol KOZANOĞLU1

Department of Plastic, Reconstructive, and Aesthetic Surgery, Istanbul University, Faculty of Medicine, Istanbul – Turkiye

 

 

Dr. Işıl İrem TURAN

İstanbul Üniversitesi Tıp Fakültesi,

Plastik, Rekonstrüktif ve Estetik Cerrahi Anabilim Dalı,

İstanbul – Türkiye

e-mail: isilturan@istanbul.edu.tr

 

 

Dr. Ömer Faruk AKPINAR

İstanbul Üniversitesi Tıp Fakültesi,

Plastik, Rekonstrüktif ve Estetik Cerrahi Anabilim Dalı,

İstanbul – Türkiye

e-mail: farukomerakpinar@gmail.com

 

 

Op. Dr. Erol KOZANOĞLU      

İstanbul Üniversitesi Tıp Fakültesi,

Plastik, Rekonstrüktif ve Estetik Cerrahi Anabilim Dalı,

İstanbul – Türkiye

e-mail: erol.kozanoglu@istanbul.edu.tr

 

 

Introduction and Aim

Basal cell carcinoma (BCC) is the most common type of skin cancer (1).  In the etiology of BCC, there are multiple factors like UV exposure, light skin color, radiotherapy, immune deficiency, HIV infection, immune-suppressant treatments, and various genetic syndromes.  UV exposure is the most important risk factor.  Among more than 26 subtypes of BCC, nodular, micronodular, superficial, morpheaform, infiltrative, and fibroepithelial BCC are the most frequent ones.  Despite the precise definitions of these subtypes, the specific etiology of their differentiation is still unknown. (1-3)

The complete blood count (CBC) test is a cheap and easy way of monitoring the immune system components present in the peripheral blood. Inflammatory markers like the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and pan-immune-inflammation ratio (PIV) can be calculated via CBC test results. The NLR is when the neutrophil count (103/mm3) divided by the lymphocyte count (103/mm3) and the platelet count (103/mm3) over the lymphocyte count (103/mm3) gives the PLR. (4) The pan-immune-inflammation value (PIV) is calculated with the formula: (the neutrophil count  (103/mm3) x platelet count (103/mm3) x monocyte count (103/mm3)) / lymphocyte count (103/mm3). (2, 5) The interactions between the immune system and various types of cancers have been elucidated with basic immunologic markers such as neutrophil and platelet lymphocyte ratios (NLR, PLR) and pan-immune-inflammation value (PIV).(6)

       In this study, the NLR, PLR, and PIV of patients with nodular, superficial, and morpheaform BCC’s were compared in order to find a differentiating effect of the immune system over the basal cell carcinoma subtypes.

 

Materials and Methods

       The study proposal was presented at the October 2023 meeting of the Clinical Research Ethics Committee of our institution, and it was ethically approved by the committee with the approval number 2023/125.  

        The study was designed as a retrospective study conducted on the patients who had been operated on for BCC between January 2019 and December 2022 at our institution, having the pathological subtype approval given by the Pathology Department of the same institute and CBC test taken in the preoperative 2-week-interval, when the patient had not had an overt infection clinic. All ages and genders were included. All patients were informed about the study and their informed consent was obtained.

        Electronic patient files were used. The patients were grouped according to the pathologically approved subtypes (nodular, superficial, and morpheaform) and looked for their PLR, NLR, and PIV values from preoperative 2-week-interval complete blood count (CBC) results. 

            The R version 2.15.3 program (R Core Team, 2013) was used for statistical analysis. In reporting the data collected from the study; the median, first quarter, and third quarter were used. The congruity of the quantitative data to normal distribution was evaluated via Shapiro-Wilk Test and graphical methods. The variables that were incongruent with normal distribution were evaluated via Kruskal-Wallis Test when more than two groups were evaluated.  Fisher-Freeman-Halton Exact Test was used in the comparison of the qualitative variables. A p-value lower than 0,05 was accepted as statistically significant.

 

Results

       A total of 38 patients, 24 female (%63,15) and 14 male (%36,85), who possessed all the inclusion criteria were grouped into three. The nodular type BCC group had 10 female (%66,7) and 5 male (%33,3); the superficial type BCC group had 7 female (%53,8) and 6 male (%46,2); and the morpheaform type BCC group had 7 female (%70) and 3 male (%30) patients. Out of 15 nodular, 13 superficial, and 10 morpheaform type BCC cases, all three groups had female dominance. (Table 1)

       There was also, statistical significance between the ages of the three groups (p:0,028). Medians of the age of the groups were 64 years, 57 years, and 75 years, respectively. With a median of age of 75 years, the morpheaform type BCC group was older than the superficial type BCC group, with a p-value of 0,023. (Table 1).

Among the immunological values evaluated in this study; the platelet value of the morpheaform type BCC cases was less than that of the nodular and the superficial type BCC with a p-value of 0,043 and 0,021 respectively. Also, the PIV value of the morpheaform type BCC cases was less than that of the nodular and the superficial type BCC cases ( p: 0.046 and p:0.020, respectively). But, there was no statistically significant difference among the three groups regarding the neutrophil count, the lymphocyte count, the NLR, and the PLR (p>0.05). (Table 2)

 

Table 1.  Age and Sex Comparison of Nodular, Superficial, and Morpheaform BCC 

 

NODULAR BCC

Median (Q1, Q3)

SUPERFICIAL BCC

Median (Q1, Q3)

MORPHEAFORM BCC

Median (Q1, Q3)

Test Value (χ2 )

P

Age

64 (57, 73)

57 (54, 70)

75 (70, 77)

a7.133

0.028*

n (%) 

n (%) 

n (%) 

Sex

b0.802

758

Female

10 (66.7)

7 (53.8)

7 (70)

Male

5 (33.3)

6 (46.2)

3 (30)

 

aKruskal-Wallis Test results are presented as median (first quarter, third quarter).

Fischer-Freeman-Halton Exact Test

*p<0.05

 

 

 

 

Table 2  CBC Parameters, NLR, PLR, and PIV of Nodular, Superficial, and Morpheaform BCC

 

NODULAR BCC

Median (Q1, Q3)

SUPERFICIAL BCC

Median (Q1, Q3)

MORPHEAFORM BCC

Median (Q1, Q3)

Test Value (χ2 )

P

Trombocyte

256000 (224000, 289000)

269000 (230000, 286000)

189000 (176000, 243000)

6.001

0.049*

Neutrophil

4600 (3800, 5400)

4800 (3250, 5500)

3540 (2600, 4620)

3.269

195

Lymphocyte

2000 (1500, 2200)

2100 (1800, 2400)

1960 (1450, 2300)

1.575

455

Monocyte

500 (400, 600)

600 (600, 660)

500 (400, 500)

4.536

103

NLR

2.45 (1.58, 3.81)

2.29 (1.44, 3.24)

1.99 (1.17, 2.41)

1.682

431

PLR

140 (90, 187.06)

127.78 (84.96, 152.11)

111.75 (78.7, 143.5)

1.933

380

PIV

301466666.7            

(179200000, 445885714.3)

304137026.2           

(205920000, 486736842.1)

159091666.65  

(133189189.2, 204722222.2)

6.041

0.049*

 

Kruskal-Wallis Test results are presented as median (first quarter, third quarter).

*p<0.05

 

4  Discussion and Conclusion

To assess the relationship between the immune system and various cancer types, many compound scores derived from CBC indices like neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), pan-immune-inflammation value (PIV) and systemic-immune-inflammation index (SII) are being evaluated as indirect measures of inflammatory burden in cancer (2, 6).  In a study conducted on metastatic melanoma patients receiving first-line therapy, high PIV was linked to resistance to both immunotherapy and targeted therapy as well as poor overall survival and progression-free survival. (5)  

The immune system plays a significant role also in the tumorigenesis and prognosis of skin cancer. (5-8) Neutrophil, monocyte, WBC, and NLR levels in skin cancer patients were found to be lower than that of the healthy group. (6) High NLR and PLR levels correlate to poor outcomes in melanoma patients. (9, 10) High PLR and SII values are also, correlated with the presence of metastatic lymph nodes. (2) These immunologic parameters were also investigated about their ability to differentiate skin cancer types from one another.  Neutrophil to lymphocyte ratio (NLR) is found to be the lowest in BCC among skin cancers. (6)  According to the study done by Derebaşınoğlu et al., NLR value was found to be ineffective in the differential diagnosis of malignant melanoma from SCC and BCC. (2) In the same study, it was found that SCC patients had higher NLR, PRL, and SII values compared to the BCC group. (2)

        To the best of our knowledge, no prior studies have been conducted on PLR, NLR, and PIV values in different BCC subtypes. 

The inability to determine a cut-off value for platelet count and PIV, and the effect of various factors like age, sex, infectious, and other inflammatory reasons on CBC parameter results are the weaknesses of this study. Also, new studies conducted on the presence and number of different immune cells at excisional biopsy specimens are needed to better understand the features of the different BCC subtypes.

The results of this study are not concordant with the literature since high platelet count and PIV are correlated with poor results whereas the worst basal cell carcinoma subtype, morpheaform BCC, had lower platelet count and PIV than the other two.

 

Disclosure

      None of the authors have a financial relationship with any institutions, individuals, or organizations. 

 

 

 References

 

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2.         DEREBAŞINLIOĞLU H, Demir H, Karaca SN. The Role of Inflammatory Markers in the Differential Diagnosis of Skin Cancers. Journal of Contemporary Medicine. 2022;12(5):761-9.

3.         Jayaraman SS, Rayhan DJ, Hazany S, Kolodney MS. Mutational landscape of basal cell carcinomas by whole-exome sequencing. Journal of Investigative Dermatology. 2014;134(1):213-20.

4.         Kozanoğlu E, Mete FS, Özkan AÇ. Investigation of the Differences between the Immunity of High-and Low-risk Anatomical Regions in Patients with Basal Cell Carcinoma: Is Neutrophil to Lymphocyte Ratio Associated with Regional Distribution of the Tumor? Turkish Journal of Oncology/Türk Onkoloji Dergisi. 2020;35(2).

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8.         Li B, Zhou P, Liu Y, Wei H, Yang X, Chen T, et al. Platelet-to-lymphocyte ratio in advanced cancer: review and meta-analysis. Clinica Chimica Acta. 2018;483:48-56.

9.         Wade RG, Robinson AV, Lo MC, Keeble C, Marples M, Dewar DJ, et al. Baseline neutrophil–lymphocyte and platelet–lymphocyte ratios as biomarkers of survival in cutaneous melanoma: a multicenter cohort study. Annals of Surgical Oncology. 2018;25:3341-9.

10.       Zhang F, Gong W. Prognostic value of the platelet-to-lymphocyte ratio in patients with melanoma: a meta-analysis. Frontiers in Oncology. 2020;10:1116.