Clinical Impact of Elastic Laminal Invasion in Colon Cancer

Yokota, Mitsuru; Kojima, Masaru; Nomura, Shosaku; Nishizawa, Yusuke; Kobayashi, Akihiro; Ito, Masaaki; Ochiai, Atsushi; Saitô, Norio

doi:10.1097/dcr.0000000000000124

Cited by 17 publications

(11 citation statements)

References 28 publications

(30 reference statements)

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“…Embedded within the connective tissue, the peritoneal elastic lamina (PEL) has been identified [2,3]. In patients with colon carcinoma, tumor invasion with an intact PEL has been associated with increased survival compared to tumor invasion with a fragmented PEL [4,5]. However, for peritoneal metastases of EOC, the prognostic relevance of the PEL and their correlation with depth of metastatic tumor invasion is unknown.…”

Section: Introductionmentioning

confidence: 99%

The effect of the peritoneal tumor microenvironment on invasion of peritoneal metastases of high-grade serous ovarian cancer and the impact of NEOADJUVANT chemotherapy

et al. 2020

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Introduction. Peritoneal metastases of high-grade serous ovarian cancer (HGSOC) are small-sized deposits with superficial growth towards the peritoneal cavity. It is unknown whether integrity of the peritoneal elastic lamina (PEL) correlates with the peritoneal tumor microenvironment (pTME) and whether neoadjuvant chemotherapy (NACT) affects the pTME. We explored integrity of PEL, composition of pTME, effects of NACT, and the prognostic implications in patients with extensive peritoneal metastases of HGSOC. Methods. Peritoneal samples (n=69) were collected during cytoreductive surgery between 2003-2016. Clinical data were collected from medical charts. Integrity of PEL was evaluated with elastic stains. Tcell (CD3, CD8) and M2-macrophage markers (CD163) were scored using algorithms created in Definiens Tissue studio. Results. Patients with a disrupted PEL (n=39; 57%), more often had residual disease after surgery (p=0.050), compared to intact PEL. An intact PEL was associated with increased intraepithelial (ie)CD8+ cells (p=0.032), but was not correlated with improved survival. After NACT, decreased stromal (s)CD3+ cells were shown, compared to no-NACT (p=0.044). Abundance of total CD3+ and CD8+ cells were associated with PFS (multivariate HR 0.40; 95%CI 0.23-0.69 and HR 0.49; 95%CI 0.29-0.83) and OS (HR 0.33; 95%CI 0.18-0.62 and HR 0.36; 95%CI 0.20-0.64). M2-macrophage infiltration was not correlated with survival. Conclusion. NACT decreases abundance of sCD3+ cells in peritoneal metastases of HGSOC. Increase of CD3+ and CD8+ cells is associated with improved PFS and OS. This suggests that CD3+ and CD8+ cells may function as prognostic biomarkers. Their role as predictive biomarker for chemotherapy or immunotherapy response in HGSOC warrants further research.

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Section: Introductionmentioning

confidence: 99%

The effect of the peritoneal tumor microenvironment on invasion of peritoneal metastases of high-grade serous ovarian cancer and the impact of NEOADJUVANT chemotherapy

et al. 2020

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“…ET stains can also highlight the peritoneal elastic lamina which provides a useful landmark when the serosa is obscured by a desmoplastic or fibro-inflammatory reaction; moreover, there is emerging evidence that penetration beyond the peritoneal elastic lamina may be associated with adverse outcomes in pT3 CRC. [35][36][37][38][39] Four pathologists indicated that PNI was easier to evaluate on ET than H&E, possibly due to the improved contrast between the nerves (dusty light green-blue) and muscularis propria (brown-red), whereas only 2/10 observers found PNI easier to evaluate on H&E (4 reported no difference between the 2 stains). Nonetheless, neither accuracy nor reproducibility of pT stage or PNI differed between H&E and ET sections.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, 8 of 10 observers considered the ease of assessment of T-stage to be at least equivalent on ET compared with H&E, with 4 considering ET to be the superior stain for this assessment. ET stains can also highlight the peritoneal elastic lamina which provides a useful landmark when the serosa is obscured by a desmoplastic or fibro-inflammatory reaction; moreover, there is emerging evidence that penetration beyond the peritoneal elastic lamina may be associated with adverse outcomes in pT3 CRC 35–39. Four pathologists indicated that PNI was easier to evaluate on ET than H&E, possibly due to the improved contrast between the nerves (dusty light green-blue) and muscularis propria (brown-red), whereas only 2/10 observers found PNI easier to evaluate on H&E (4 reported no difference between the 2 stains).…”

Section: Discussionmentioning

confidence: 99%

Feasibility and Performance of Elastin Trichrome as a Primary Stain in Colorectal Cancer Resection Specimens

Shivji

Kak

Reid

et al. 2021

American Journal of Surgical Pathology

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Venous invasion (VI) is a powerful prognostic factor in colorectal cancer (CRC) that is widely underreported. The ability of elastin stains to improve VI detection is now recognized in several international CRC pathology protocols. However, concerns related to the cost and time required to perform and evaluate these stains in addition to routine hematoxylin and eosin (H&E) stains remains a barrier to their wider use. We therefore sought to determine whether an elastin trichrome (ET) stain could be used as a “stand-alone” stain in CRC resections, by comparing the sensitivity, accuracy, and reproducibility of detection of CAP-mandated prognostic factors using ET and H&E stains. Representative H&E- and ET-stained slides from 50 CRC resections, including a representative mix of stages and prognostic factors, were used to generate 2 study sets. Each case was represented by H&E slides in 1 study set and by corresponding ET slides from the same blocks in the other study set. Ten observers (3 academic gastrointestinal [GI] pathologists, 4 community pathologists, 3 fellows) evaluated each study set for CAP-mandated prognostic factors. ET outperformed H&E in the assessment of VI with respect to detection rates (50% vs. 28.6%; P<0.0001), accuracy (82% vs. 59%, P<0.0001), and reproducibility (k=0.554 vs. 0.394). No significant differences between ET and H&E were observed for other features evaluated. In a poststudy survey, most observers considered the ease and speed of assessment at least equivalent for ET and H&E for most prognostic factors, and felt that ET would be feasible as a stand-alone stain in practice. If validated by others, our findings support the use of ET, rather than H&E, as the primary stain for the evaluation of CRC resections.

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“…Peritoneal elastic lamina, located immediately beneath the basement membrane of mesothelial cells, can be a landmark for assessing tumor spread in colon cancer. Peritoneal elastic laminal invasion (ELI) detected using elastic staining can reportedly be a prognostic factor in pT3 and pT4a colon cancer and can be introduced in pT classification, similar to that in lung cancer 11–20 . Furthermore, various studies have presented several arguments regarding the introduction of elastic staining in routine pathologic practice, in terms of the 21–23 : (1) adequate sample number for elastic staining, (2) adequate method for elastic staining, (3) assessment of cases without obvious elastic lamina, and (4) reproducibility as a prognostic factor.…”

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confidence: 99%

Assessment of Elastic Laminal Invasion Contributes to an Objective pT3 Subclassification in Colon Cancer

Kojima

Yokota²,

Yanagisawa

et al. 2023

American Journal of Surgical Pathology

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The extent of tumor spread influences on the clinical outcome, and which determine T stage of colorectal cancer. However, pathologic discrimination between pT3 and pT4a in the eighth edition of the American Joint Committee on Cancer (AJCC)-TNM stage is subjective, and more objective discrimination method for deeply invasive advanced colon cancer is mandatory for standardized patient management. Peritoneal elastic laminal invasion (ELI) detected using elastic staining may increase the objective discrimination of deeply invasive advanced colon cancer. In this study, we constructed ELI study group to investigate feasibility, objectivity, and prognostic utility of ELI. Furthermore, pT classification using ELI was investigated based on these data. At first, concordance study investigated objectivity using 60 pT3 and pT4a colon cancers. Simultaneously, a multi-institutional retrospective study was performed to assess ELI’s prognostic utility in 1202 colon cancer cases from 6 institutions. In the concordance study, objectivity, represented by κ, was higher in the ELI assessment than in pT classification. In the multi-institutional retrospective study, elastic staining revealed that ELI was a strong prognostic factor. The clinical outcome of pT3 cases with ELI was significantly and consistently worse than that of those without ELI. pT classification into pT3 without ELI, pT3 with ELI, and pT4a was an independent prognostic factor. In this study, we revealed that ELI is an objective method for discriminating deeply invasive advanced colon cancer. Based on its feasibility, objectivity, and prognostic utility, ELI can subdivide pT3 lesions into pT3a (without ELI) and pT3b (with ELI).

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Clinical Impact of Elastic Laminal Invasion in Colon Cancer

Cited by 17 publications

References 28 publications

The effect of the peritoneal tumor microenvironment on invasion of peritoneal metastases of high-grade serous ovarian cancer and the impact of NEOADJUVANT chemotherapy

The effect of the peritoneal tumor microenvironment on invasion of peritoneal metastases of high-grade serous ovarian cancer and the impact of NEOADJUVANT chemotherapy

Feasibility and Performance of Elastin Trichrome as a Primary Stain in Colorectal Cancer Resection Specimens

Assessment of Elastic Laminal Invasion Contributes to an Objective pT3 Subclassification in Colon Cancer

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