Clinicopathological Features And Molecular Pathology Of Colorectal Mucinous Adenocarcinoma

Background:Because of their rare occurrence,clinicopathological characteristics of MAC and SRCC were still in veil and concrete evidence of biological nature of MAC and SRCC lacked.Since the theory of second strike was discovered in the progression of colorectal adenoma to adenocarcinoma by Fearon and Vogelstein in 1990,multiple molecular genetics alteration was discovered and identified.Plenty of genetic alterations had already been verified that most of them was involved in the initiation and progression of CRC Besides,multiple genetic alteration and gene mutation were also discovered,including chromosome instability(CIN),mismatch repair(MMR),CpG island methylation phenotype and some driver mutations,such as KRAS,BRAF and SMAD4,etc.As the development of next generation sequencing(NGS),not only were the molecular genetic alterations in CRC detected by traditional molecular biological technologies,such as polymerase chain reaction and immunohistochemical staining(IHC),but also could be examined by newborn technology.NGS has a higher efficiency and accuracy to detect the genome.Therefore,the study selected one hundred and one MAC and carried on IHC,PCR and NGS to identify the characteristics,analyzed the relationship between genetic alterations and clinicopathological characteristics.Then we analyzed the genetic alteration profiles of CRC that detected by NGS to increase the understanding of genetic alterations in CRC with or without signet ring cells.Methods:The study included one hundred and one CRC cases from Peking Union Medical College Hospital archive and related clinicopathological information were collected.Hematoxylin and eosin staining were carried out to identify the diagnosis of MAC and differentiation of signet ring cells.Immunohistochemical staining and specific staining were carried for assistant diagnosis of MAC.Appropriate areas of MAC were selected and scraped to purify DNA and detected the genome mutation profiles by NGS to search for the relationship between genetic alterations and clinicopathological characteristics in CRC with or without signet ring cells.Results:One hundred and one included cases consist of fifteen MAC with signet ring cells(14.9%)and 86 MAC without signet ring cells.Fifty-nine males and 42 females were included Fourth patients were less than 55 years old,47 were between 56 and 75 years old and 14 were more than 76 years old.Forty-four tumors located in the proximal colon while 57 cases were in the distal colon.Fifty cases showed a less than 5 cm diameter of tumor.Clinical stages consist of 10 in stage ?,32 in stage ?,49 in stage ? and 8 in stage IV.Two cases were not classified because of lack of essential information.No significant differences of ages,gender,tumor location,and tumor staging between MAC with and without signet ring cells,while differentiation of signet ring cells were associated with smaller tumor volume of MAC(P=0.01).KRAS mutation was discovered in 46 cases(45.5%)and the most frequent type was exon 2 G12D(26.1%),following the other three mutation types,G12V(23.9%),G13D(19.6%)and A146T(15.2%).MAC without signet ring cells showed a higher KRAS mutation than MAC with signet ring cells(P=0.001).Clinicopathological characteristics showed no significant differences between the KRAS and BRAF mutated and wild type MAC.Conclusion:1.Tumor volume in MAC with signet ring cells was smaller than MAC without signet ring cells.2.There may be difference at molecular level between MAC with signet ring cells and MAC without signet ring cells.