Back to the start: Evaluation of prognostic markers in gastrointestinal stromal tumors

Abstract

Abstract. The aim of this study was to provide a standardized risk stratification model for gastrointestinal stromal tumors (GISTs) based on tumor localization, tumor size, involved lymph nodes and metastases, as well as mitotic activity and other morphological and molecular markers, in order to improve the risk evaluation scheme for recurrence, metastatic spread and survival for patients with GIST. A total of 201 cases of patients with GIST were investigated according to standardized morphological markers, including nuclear pleomorphism, tumor cell necrosis, mucosal infiltration, ulceration, skeinoid fibers and growth pattern. In addition, all cases were immunohistochemically analyzed using a tissue microarray platform for various markers of differentiation (CD34, CD44, CD117, desmin, discovered on GIST 1, platelet-derived growth factor receptor α, S-100 and smooth muscle actin) and proliferation (B-cell lymphoma 2, P16, P53, phosphohistone H3 and Ki-67). These findings were correlated by uni-and multivariable analyses with clinicopathological characteristics, including recurrence, metastasis and survival. The general clinicopathological parameters of this GIST specimen cohort were comparable to previous studies. While several parameters exhibited clear associations to each other and to the defined clinical endpoints, the multivariate analysis reduced the number of relevant prognostic variables to localization, margin status, growth pattern and hematoxylin and eosin-based mitosis̸Ki-67-based proliferation of GISTs. With the exception of CD34, none of the applied markers of differentiation and proliferation were found to be independent prognostic markers in GIST and the classical risk factors of GIST remain important prognostic factors. Additionally, growth pattern may predict the risk of recurrence and metastasis in GIST patients. Additional independent molecular prognostic markers remain to be identified and validated.

Gastrointestinal stromal tumor: clinicopathological characteristics and pathologic prognostic analysis

“…This observation was in agreement with that of Ahmed et al [9], Klieser et al [10], Lopes et al [11] Alqusous et al [12], Vij et al [13], Yacob et al [14], Din et al [16], Li et al [17], Cao et al [18], Sui et al [19], Tazawa et al [20], Kang et al [21], and Kkrishnappa et al [22]. These are in contrast with the two studies of Antonescu et al [7] and Bhalgami et al [15] which found slightly more in the small intestine than stomach.…”

“…One of the studies conducted in Pakistan, Din et al [16], one from China, Sun et al [19], and one from Korea, Kang et al [21], also found that majority were spindle type (84.7%, 83%, 88.2%), followed by epithelioid cell type (12.5%, 10%, 9.3%), and the minority were mixed spindled-epithelioid cell type (2.7%, 8%, 2.5%). However, the study of Klieser et al [10] in Europe found that the majority were spindle type (61.2%), while the epithelioid cell type (19.4%) was equally found with the mixed spindled-epithelioid cell type (19.4%).…”

“…On the contrary, most of the other studies showed males were slightly affected than females including Antonescu et al [7], Alqusous et al [12], Din et al [16], and Tazawa et al [20]. However, two other series had reported a higher incidence in females compared to males [Eckhard Klieser et al [10] and Yu Na Kang et al [21]].…”

Gastrointestinal stromal tumors: a clinicopathological and immunohistochemical study of 65 cases

“…GISTs can occur at every level of the gastrointestinal tract, but most commonly in the stomach (60-70%), and small intestine (20-30%). Rarely, they can be seen in extragastrointestinal locations, like the omentum, retroperitoneum, and mesentery (1)(2)(3)(4)(5)(6)(7). GISTs occur by neoplastic transformation of the interstitial cell of Cajal, the mesenchymal derived intestinal pacemaker cells (1)(2)(3)(4).…”

“…These cells specifically express the tyrosine kinase receptor c-kit (CD 117). Although several GISTs show strong histomorphological similarities, they have different immunophenotypes and biological behavior, and this diversity yields various confusing data in the literature (1)(2)(3)(4)(5)(6)(7). The purpose of this study was to determine the clinicopathologic features of 65 GISTs and reveal the pathological factors that negatively influence overall survival.…”