J Pathol Transl Med.  2018 Sep;52(5):323-330. 10.4132/jptm.2018.07.21.

Significance of Intratumoral Fibrosis in Clear Cell Renal Cell Carcinoma

• Joung JW
• Oh HK
• Lee SJ
• Kim YA
• Jung HJ

• KMID: 2422099
• DOI: http://doi.org/10.4132/jptm.2018.07.21

Abstract

BACKGROUND
Intratumoral fibrosis (ITF) is a frequent histologic finding in solid organ tumors. Renal cell carcinoma (RCC) is a highly vascularized tumor with different shapes and degrees of ITF and inflammation. ITF is a poor prognostic factor, especially in breast cancer, and is related to intratumoral necrosis (ITN) and intratumoral inflammation (ITI). However, the significance of ITF in RCC has not been fully studied. In this study, we evaluate the relationships between ITF and other clinicopathologic parameters associated with RCC prognosis.
METHODS
ITF was evaluated in 204 clear cell renal cell carcinoma (CCRCC) specimens according to presence and grade of fibrosis, degree of ITI, and presence of ITN. Lysyl oxidase (LOX) expression in tumor cells was also evaluated with clinicopathologic parameters.
RESULTS
Among 204 CCRCC cases, 167 (81.7%) showed ITF, 71 (34.8%) showed ITI, 35 (17.2%) showed ITN, and 111 (54.4%) showed LOX expression. ITF correlated with Fuhrman nuclear grade (p = .046), lymphovascular invasion (LVI) (p = .027), and ITN (p = .036). Patients with ITF had a poor five-year overall survival rate (p = .104).
CONCLUSIONS
ITF is related to other poor prognostic factors in CCRCC, such as Fuhrman nuclear grade, ITN, and LVI, but ITF itself had no significant correlation with prognosis of CCRCC.

Keyword

Carcinoma, renal cell; Fibrosis; Inflammation; Protein-lysine 6-oxidase

MeSH Terms

Breast Neoplasms
Carcinoma, Renal Cell*
Fibrosis*
Humans
Inflammation
Necrosis
Prognosis
Protein-Lysine 6-Oxidase
Survival Rate
Protein-Lysine 6-Oxidase

Figure

• 

  Fig. 1. Intratumoral fibrosis (ITF). Hematoxylin and eosin staining is compared with trichrome staining. (A, B) Grade 1 ITF mainly composed of loose connective tissue. (C, D) Grade 2 ITF composed of collagen fibers and loose connective tissue. (E, F) Grade 3 ITF mainly composed of sclerotic collagen fibers.

• 

  Fig. 2. Intratumoral inflammation (ITI). (A) Grade 1 ITI with scattered inflammatory cells. (B) Grade 2 ITI with focal aggregation of inflammatory cells. (C) Grade 3 ITI with diffuse or nodular aggregation of inflammatory cells.

• 

  Fig. 3. Immunohistochemical staining of lysyl oxidase (LOX). (A) Control staining of normal kidney. Tubular cells show no reactivity. (B) LOX expression 1, with focal and weak staining in tumor cell cytoplasm. (C) LOX expression 2, with moderate cytoplasmic staining in nearly 50% of tumor cells. (D) LOX expression 3, with strong and diffuse staining of tumor cell cytoplasm.

• 

  Fig. 4. 5-Year overall survival rate according to intratumoral fibrosis.

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