Clinicopathological differences, risk factors and prognostic scores for western patients with intestinal and diffuse-type gastric cancer

Abstract

BACKGROUND In the molecular era, the Laurén system is still a cost-effective and widely implemented classification for gastric cancer (GC) and it has been recently associated with clinical, histological and molecular features of these tumors. Despite recent advances in the understanding of the molecular biology of GC, there is a need to develop new prognostic tools for patient stratification in clinical practice. Thus, the identification of easily available prognostic factors in patients with intestinal and diffuse-type tumors can significantly improve risk assessment and patient stratification in GC. AIM To identify clinicopathological differences, risk factors, and to develop cost-effective prognostic scores for patients with intestinal and diffuse-type GC. METHODS Retrospective study of all patients undergoing surgery for GC at a tertiary referral center from 2001 to 2019. 286 cases met inclusion criteria (intestinal: 190, diffuse: 96). Clinical data and gross findings were collected. All specimens were reviewed by two independent pathologists and a detailed protocol for histologic evaluation was followed. Five tissue microarrays (TMAs) were constructed and sections of the TMA block were immunostained for HERCEPTEST, MSH2, MSH6, MLH1 and PMS2. Statistical analyses were performed and prognostic scores were developed based on hazard ratios. RESULTS Intestinal and diffuse-type GC showed different epidemiological, clinicopathological and prognostic features. Diffuse tumors were significantly associated with younger age, less symptomatology, flat morphology, deeper invasion, perineural infiltration, advanced stage at diagnosis, administration of adjuvant therapy and poorer prognosis. Intestinal lesions were fungoid or polypoid, showed necrosis, desmoplasia, microsatellite instability and HERCEPTEST positivity and were diagnosed at earlier stages. Tumor depth, desmoplasia, macroscopic type and lymph node involvement were independently related to the Laurén subtype. Furthermore, intestinal and diffuse GC were associated with different risk factors for progression and death. Vascular invasion, perineural infiltration and growth pattern were important prognostic factors in intestinal-type GC. On the contrary, tumor size and necrosis were significant prognosticators in diffuse-type GC. Our recurrence and cancer-specific death scores for patients with intestinal and diffuse-type GC showed an excellent patient stratification into three (diffuse GC) or four (intestinal) prognostic groups. CONCLUSION Our findings support that Laurén subtypes represent different clinicopathological and biological entities. The development of specific prognostic scores is a useful and cost-effective strategy to improve risk assessment in GC.

Liquid biopsy for gastric cancer: Techniques, applications, and future directions

“…According to the Laurén classification, described in 1965 and still used in clinical practice, GC can be divided into intestinal, diffuse, and mixed types[ 127 ]. As observed by our research team in a previous study, supporting findings from other investigators, there are differences in clinical, molecular, and prognostic characteristics between intestinal and diffuse GC[ 128 ]. Therefore, studying Laurén subtypes separately could enhance patient stratification both in clinical practice and in clinical trials.…”

Epstein-Barr virus in gastric cancer and association with 30 bp del-latent membrane protein 1 polymorphism

“…Nonetheless, the poorer prognosis presented for EBV-positive patients found in our investigation may perhaps be explained by the fact that, in this sample, there were 27 tumors of the diffuse type against only 10 of the intestinal type and one with both. In the literature, it has been reported that diffuse tumors have a worse prognosis than intestinal ones 19 , 20 .…”

High Expression of THY1 in Intestinal Gastric Cancer as a Key Factor in Tumor Biology: A Poor Prognosis-Independent Marker Related to the Epithelial–Mesenchymal Transition Profile

“…Malanchi et al (2011) found that cancer stem cells expressing THY1 respond to increased matrix components at metastatic sites [71]. Moreover, Díaz Del Arco et al (2022) showed that desmoplasia, a fibrotic process resulting from accumulation of extracellular matrix components, is associated with intestinal gastric cancer when compared to the diffuse type [72]. The Thy-1 protein, encoded by the THY1 gene, is involved in mechano-signaling, a pathway that results from interaction with matrix components [73,74].…”