Dermatology Reports 2019; volume 11(s1):8012 The role of protein-53 amyloid bFGF have an important role in BCC aggre- in determining the aggressive- sivity. Correspondence: Prasetyadi Mawardi, Departement of Dermatovenerology, Dr. ness of basal cell carcinoma Moewardi General Hospital, Surakarta, regulated by interleukin-6, Indonesia. Introduction Tel.: +62271 634 848 - Fax: +62271 634 848. myeloid cell leukemia-1 and E-mail: [email protected] basic fibroblast growth factor Basal cell carcinoma (BCC) is a very Key words: basal cell carcinoma, basic fibrob- common malignant skin tumor that rarely last growth factor, protein-53 amyloid, inter- leukin-6, myeloid cell leukimia-1 Prasetyadi Mawardi,1 Handono Kalim,2 metastasizes, even though is often locally 3 aggressive. Several factors, like a large size Kusworini Handono Kalim, Contributions: The authors contributed equally. Loeki Enggar Fitri,4 (more than 3 cm), face localization, expo- sure to ultraviolet rays, histological vari- Karyono Mintarjo,5 Ambar Mudigdo,6 Conflict of interest: the authors declare no ants, infiltration level and perineural or Oyong Oyong,6 Brian Wasita6 potential conflict of interest. perivascular invasion, are associated with a 1 1 Dermatovenereology Department, more aggressive clinical course. Although Received for publication: 1 February 2019. Medical Faculty of Sebelas Maret it rarely metastasizes, BCC can cause sig- Accepted for publication: 6 February 2019. University/Dr. Moewardi Public nificant damage due to its local and aggres- 2 Hospital, Surakarta; sive recurrences. p53 is activated upon the This work is licensed under a Creative 2 induction of DNA damage to either arrest Commons Attribution-NonCommercial 4.0 Internal Medicine Department, Faculty International License (CC BY-NC 4.0). of Medicine Brawijaya University/dr. the cell cycle or to induce apoptosis. Saiful Anwar Public Hospital, Malang; However, when mutated, p53 is no longer ©Copyright P. Mawardi et al., 2019 3 able to properly accomplish these functions. Clinical Pathology Department, Faculty Licensee PAGEPress, Italy Apparently, appropriate p53 functioning is of Medicine Brawijaya University/dr. Dermatology Reports 2019; 11(s1):8012 crucial for the suppression of tumor devel- doi:10.4081/dr.2019.8012 Saiful Anwar Public Hospital, Malang; 3 only 4 opment. The p53 gene is not reactive in Parasitology Department, Faculty of cells where DNA is undamaged. When Medicine Brawijaya University/dr. there is DNA damage, the gene suspends by two expert pathologists who agreed on Saiful Anwar Public Hospital, Malang; the cell cycle until the damage can be all specimens involved in the study. 5Pathology Department, Faculty of repaired. The p53 gene is not reactiveuse in Histopathological types of BCC were deter- Medicine, Brawijaya University/dr. cells where DNA is undamaged. When mined and histopathological classification Saiful Anwar Public Hospital, Malang; there is DNA damage, the gene suspends of the lesions was performed according to 6Pathology Department, Medical Faculty the cell cycle until the damage can be the criteria proposed by Dixon and Jacobs 6,7 of Sebelas Maret University/Dr. repaired. If there is a mutation in p53, the et al. In order to detect p53 protein expres- Moewardi Public Hospital, Surakarta, cell cycle continues unrestrained and dam- sion in BCC specimens, we performed Indonesia aged DNA is reproduced, leading to uncon- immunohistochemical staining as follows. trolled cell proliferation and cancerous Initially, we chose adequately represented tumors.4 The existence of amyloid deposits BCC paraffin blocks, and then the blocks Abstract in BCC has been found in previous studies. were deparaffinized and dehydrated. The frequency of secondary amyloidosis in Strongly positive control slides were used Basal cell carcinoma (BCC) is a com- BCC varies from 50% to 75% in the litera- in each run of the immunochemical staining mon malignant skin tumor that rarely ture. In the past, the origin of amyloid in procedure for each protein, i.e. p53 (breast metastasized, although it is often locally BCC was thought to be derived from degen- carcinoma), IL-6 (tonsil) and bFGF (brain destructive and aggressive. The amyloid in erated epithelial cells following apoptosis.5 tissue). Expression measurement of p53, Il- BCC is resulted from degenerated epithelial This study aimed to investigate the dif- 6, MCl-1, and bFGF and p53 amyloid used cell through apoptosis caused by activation ferences in the immunohistochemical J-Image (open access). Amyloid deposite of p53. Interleukin-6, MCL-1 and bFGF are Non-commercialexpression of p53, amyloid deposits, IL-6, were assessed with the Congo Red staining inflammatory mediators which have impor- MCL-1 and bFGF in aggressive BCC. The procedure. Statistical analyzed with tant role in angiogenesis. To prove that high expression of these markers was associated Kruskal Wallis and Mann Whitney method expression of p53 amyloid is related to with clinicopathological features such as for comparing data, and Pearson’s chi aggressiveness of BCC via the regulation of age, gender and anatomical sites of the square for correlation studied. IL-6, MCL-1 and bFGF expression. lesions, as well as aggressive vs non- Archived specimens from 51 cases diag- aggressive forms of BCC. nosed with Primary BCC. We performed immunohistochemical staining for IL-6, Results MCL-1, bFGF expression and p53 amyloid Materials and Methods From the 51 BCC pathologic’s slides deposit. There was a significant difference that underwent histopathological examina- in the expression of p53 (p = 0.04), amyloid Archived specimens from 51 cases tions, thirteen patients were excluded. In deposits (p = 0.015), P53 amyloid deposits diagnosed with primary BCC were collect- this study we found predominantly females (p = 0.038), IL-6 (p = 0.040), MCL-1 (p = ed from December 2014 to May 2016 at the than males (55.3%; 44.7%). The age range 0.032), bFGF (p = 0.044) in A BCC com- Dr. Moewardi Public Hospital in Surakarta, of the patients were 41-90 years old, with pared with NA BCC. There were a signifi- Central Java, Indonesia. Clinical findings the most common occupation was farmer cant association between MCL-1 and bFGF such as age, gender and tumor localization (53.6 %) and housewife (26.7 %). (p = 0.07) and p53 amyloid with bFGF (p = were obtained from medical records. According to the duration of illness, most 0.051). p53 amyloid, IL-6, MCL-1 and Specimens were reevaluated independently patients had symptom for more than 3 years [Dermatology Reports 2019; 11(s1):8012] [page 1] Article and affect people over 50 years old. 0.07) and contigency coefficient (cc) 0.34 stated by Baker (2007), the midface area Based on the biological aspect BCC, this This study also found a close correlation covers the glabella to the sub-nasal area.10 study has found aggressive BCC (A BCC) between p53 amyloid with bFGF (p = 0.051) According to the histological findings, the is more dominant than nonaggressive BCC and contigency coefficient (cc) 0.45. nodular, morpheic and basosquamous BCC (NA BCC) with 65.8% and 34.2 % respec- subtypes were more frequent than the other tively. All patients were divided based on subtypes in this study. The most common site predilection according to the Baker pro- subtype (with an estimated 60%-75% tocol (2007). About 73.7 % tumor site pre- Discussion prevalence overall) is the nodular (or nodu- dominant in the midface followed by the locystic) subtype, which is especially com- 11 upperface (15.8%) and the lowerface Basal cell carcinoma is the most com- mon in the head and neck area. In this mon cutaneous cancer, with increasing (10.5%). There was significant difference study, the nodular and morpheic BCC sub- prevalence especially in lighter skinned between aggressive BCC and nonaggres- types comprised 52.6% of all samples. individuals or in the Caucasian population. sive BCC upon tumor site predilection (p = Basal cell carcinoma is a multifactorial Several studies have shown that BCC is 0.033). Based on histopathological features, disease in which both environmental factors more often found in men compared to this study found 6 (six) subtype of BCC, and host genetic factors are implicated in women. This may reflect a higher rate of which are nodular, basosquamous, mor- carcinogenesis. In this study, 47.4% nuclear sun exposure in males because of their pheaform, mixed, infiltrative and superfi- positivity for p53 was found in all groups. employment pattern.8 However, in this cial subtype. Nodular and morpheaform Khodaeilani et al. (2013) found a p53 study, BCC was found more often in BCC were more dominant subtype than oth- expression rate of 67.7%, which was higher women than in men, i.e. 55.3% vs. 44.7%, 12 ers. Expression of p53 was found 76.3% in than in this study. The tumor suppressor respectively. The incidence in women is this study. This expression is higher in A p53 regulates genome integrity. It is fre- increasing due to changing fashions in quently mutated in all types of human can- BCC rather than in NA BCC (47.4% vs clothing and increased time spent outdoors 28.9%). There was a significant difference cer, making p53 a main factor in cancer for recreational or occupational reasons. development.13 Based on amyloid deposits, in the expression of p53 positive 1 and 2 A Based on occupation, this study found that BCC compared with NA BCC (p = 0.04). this study found that most BCC (92.1%) farmers are more frequently affected BCC had onlyamyloid deposits. Several previous Amyloid deposits was found in 89.4%, in than others. UV radiation, especially UVB, studies have found that secondary amyloi- which the amyloid deposits in A BCC is is responsible for the majority of cutaneous dosis in BCC varies from 50% to 75%. In higher than NA BCC (60.5% vs 28.9%). damage and is believed to be the primary the present study, the origin of amyloid There was a significant difference in posi- 9 risk factor driving tumorigenesis in BCC.usedeposits in BCC is thought to be derived tive amyloid deposits 3 and 4 at A BCC The present study found more BCC in the from degenerated epithelial cells via apop- compared to NA BCC (p = 0.015).