Clinicopathologic Association and Prognostic Value of Microcystic, Elongated, and Fragmented (MELF) Pattern in Endometrial Endometrioid Carcinoma

Abstract

Microcystic, elongated, and fragmented (MELF) pattern is seen in the invasive front of some endometrial endometrioid carcinomas. Although MELF pattern can be expected as an indicator of patient outcomes, its prognostic significance remains unclear. This study was conducted to elucidate clinicopathologic features and the prognostic impact of MELF pattern in patients with endometrial endometrioid carcinoma. We retrospectively analyzed data of 479 consecutive patients with endometrial endometrioid carcinoma that had been surgically resected. In 45 of 427 patients (11%) with low-grade endometrioid carcinoma, MELF pattern was found, but it was found in none of the 52 patients with high-grade endometrioid carcinoma. Among the patients with low-grade endometrioid carcinoma, MELF pattern was associated significantly with larger tumor size, myometrial invasion of more than 50%, advanced International Federation of Gynecology and Obstetrics stages, lymphovascular space invasion, lymph node metastasis, papillary architecture, and mucinous differentiation. However, survival analysis revealed that the patients with MELF pattern showed no significantly worse prognosis than those without MELF pattern either in disease-specific survival or in recurrence-free survival. MELF was not a significant prognosticator after adjustment for International Federation of Gynecology and Obstetrics stage (disease-specific survival [hazard ratio, 1.47; 95% confidence interval, 0.28-7.67; P=0.64], recurrence-free survival [hazard ratio, 0.98, 95% confidence interval, 0.32-2.99, P=0.98]). Immunohistochemical analysis revealed that MELF pattern was positive for p16 and p21 and almost negative for Ki-67 labeling, which suggested that tumor cells in MELF pattern were involved in growth arrest or cellular senescence. We conclude that MELF pattern could have little impact on outcomes of patients with low-grade endometrial endometrioid carcinoma.

Intramucosal colorectal carcinoma with lymphovascular invasion: clinicopathological characteristics of nine cases

“…Similar to tumour budding and PDCs in terms of patterns reflecting the loss of cell adhesion based on structural changes in gynaecological pathology, particularly at the uterine corpus, in which most tumour cells form glandular structures in low-grade endometrioid carcinoma, a pattern of 'microcystic, elongated, and fragmented (MELF)', reflecting epithelial-mesenchymal transition (EMT), has recently attracted attention because the MELF pattern has been reported to be associated with lymphovascular invasion, lymph node metastasis and poorer prognosis. [40][41][42][43] Regarding MELF pattern in endometrioid carcinoma of the uterine corpus, cancer cells often show eosinophilic cytoplasm and rounded nuclei accompanied by inflammatory reactions, including neutrophilic infiltration, 41,42 similar to our 'ERI' pattern. The 'ERI' pattern is based on cellular changes of cancers and inflammatory reactions against cancer cells, in contrast to the MELF pattern which refers only to structural changes.…”

“…In our cases, all CRCs were also of the differentiated type; however, a few glands in seven of the nine cases were accompanied by high‐grade tumour budding or the ‘ERI’ pattern, indicating relatively poorer differentiation. Similar to tumour budding and PDCs in terms of patterns reflecting the loss of cell adhesion based on structural changes in gynaecological pathology, particularly at the uterine corpus, in which most tumour cells form glandular structures in low‐grade endometrioid carcinoma, a pattern of ‘microcystic, elongated, and fragmented (MELF)’, reflecting epithelial–mesenchymal transition (EMT), has recently attracted attention because the MELF pattern has been reported to be associated with lymphovascular invasion, lymph node metastasis and poorer prognosis . Regarding MELF pattern in endometrioid carcinoma of the uterine corpus, cancer cells often show eosinophilic cytoplasm and rounded nuclei accompanied by inflammatory reactions, including neutrophilic infiltration, similar to our ‘ERI’ pattern.…”

Myoinvasive Pattern as a Prognostic Marker in Low-Grade, Early-Stage Endometrioid Endometrial Carcinoma

“…However, these data cannot be directly extrapolated to our series because these authors used a different classification system to the one described in 2013, which is now widely accepted [8]. Moreover, they have few cases within the infiltrative category, in contrast to what is widely described [9][10][11][12]. In our study, we found an association between the presence of the infiltrative glands pattern and the DFS of the patients.…”

“…Since the proper recognition of five patterns of EEC myoinvasion [8], much attention has been paid to the microcystic, elongated and fragmented glands (MELF) pattern of myoinvasion. The MELF pattern has been associated with an increased risk of lymph node metastases, but without any impact on prognosis [9,10]. In contrast, there is little published data regarding the risk of recurrence associated with any of the other patterns [11,12].…”

Case report of endometrial cancer with a microcytic, elongated, and fragmented pattern of invasion and DNA mismatch repair deficiency

“…There is evidence that a MELF‐pattern of invasion and abnormal mismatch repair protein expression are independently associated with a worse prognosis by increasing isolated tumor cell metastases and non‐isolated tumor cell metastases, respectively . However, in another study, a MELF‐pattern was only identified in low‐grade endometrioid carcinomas (most with low Ki‐67) and was not recognized as an independent risk factor. In the absence of any definitive guidelines, the conflicting data on the clinical relevance of these tumor characteristics pose a challenge for gynecologic oncologists in treatment decision making.…”