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\def\RunningAuthor{Rupanita Biswal et al.}
\firstPage{1233}
\articleType{Original Article}
\receivedDate{07 Oct 2020}
\acceptedDate{09 Nov 2020}
\revisedDate{07 Nov 2020}
\journalVolume{2020, 11 (SPL4)}
\journalDoi{ijrps.v11iSPL4.4281}
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\title{Histopathological spectrum of lower Gastro-intestinal colonoscopic biopsy lesion with special reference to Her-2/neu expression in carcinoma colon}
\author{Debahuti~Mohapatra,  
            Rupanita~Biswal\textsuperscript{*},  
            Mitu~Mohanty, 
            Prateek~Das~\\[5pt]{Department of Pathology, IMS and SUM Hospital, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India}}

\begin{abstract}
Cancer associated with colon is one of the principal risk factors from decease in women and men. Although importance growing aspect of human epidermis receptor2 (Her2) as a therapeutic target is rising its role as a biomarker in the form of predicting indicator within colorectal Cancer (CRC)is still a mystery. Present research is undertaken for evaluating the Her2/neu description in Cancer of the colon. This research comprises 256patientswith spectrum of histopathological treatment ranging from colitis to colorectal carcinoma at our department between 2015- 2017. Her2/neu Immunohistochemistry was done in the colorectal carcinoma and scores based on Ruschoff et al. Her-2 testing in gastric cancer. Out of a total number of 256 cases enrolled in our study group, the majority belonged to the age group of 40-60 years, with M: F ratio being 1.4:1. The commonest site of the lesion occurred in the rectum (43.75\%) followed by ascending colon and caecum (12.08\%). Non neoplastic lesions constituted about two third of all cases, the commonest being inflammatory bowel disease(21.48\%). In benign neoplastic lesions of tubular adenoma was the commonest type, and in malignant commonest type was colorectal adenocarcinoma NOS(64.44\%) followed by mucinous adenocarcinoma (22.22\%). Because of more prominent membranous staining observed in high grade colorectal cancers, Her2neu expression is found to be an important predictive marker of carcinoma colon, especially the adenocarcinoma, NOS. Like Breast carcinoma, target oriented therapy can be instituted especially in Her 2/neu positive high grade and metastatic tumors. 
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Colonoscopic Biopsy,\newline Inflammatory Bowel Disease,\newline Tubulovillous Adenoma,\newline Colorectal Cancer,\newline Her2/Neu
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Rupanita~Biswal~\\ Phone:\ ~\\  Email:\ rupanitabiswal@soa.ac.in
        \par}\vspace*{-11pt}\hrulefill\par{\fontsize{12}{14}\selectfont ISSN: 0975-7538}\par% 
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\section{Introduction}
A variety of inflammatory disorders affect colon and rectum, accompanying acute and chronic conditions. The non-neoplastic conditions include colitis of various etiology and bowel disease \& syndrome diverticular disorder, whereas the neoplastic disease include benign and malignant polyps along with colorectal carcinoma(CRC) \unskip~\citep{988850:21274292}. Colorectal carcinoma (CRC) is considered to be very frequently happening carcinomas \& remains a major reason for decease \unskip~\citep{988850:21274293}. Colon cancer is the third prevalent Cancer irrespective of gender predilection and was the main factor of both class incidence \& death. The rising overall incidence of colorectal cancer globally is around 3 per cent per annum \unskip~\citep{988850:21274303}. The incidence in rural areas in India is approximately half of that in urban population, less incident of CRC in our country is attributable for a diet which contains more percentage of fibres \unskip~\citep{988850:21274285}. Chemotherapy has proven to be an efficient strategy for adjuvant therapy but is still incapable of preventing recurrence in all patient \unskip~\citep{988850:21274283}. In the era of tailored therapy, monoclonal Antibody is now playing a key in the treatment of metastatic CRC \unskip~\citep{988850:21274293}.

This one goal is the transmitter of the human aspect of epidermal growth -2Her2/neu, primarily being associated with breast carcinoma. Although the comprehensive characterization in the molecular histopathogenesis of Colon cancer established ErbB2 enhancement as an effective therapeutic goal, its under-expression was related to its prediction of treatment outcomes \unskip~\citep{988850:21274288}.

HER1 human epidermal growth factor(EGFR.), (Her2/neu or ErbB2), Her-3 \& Her-4 associated with the growing aspect of human epidermal receptor family membranous bound G-protein coupled receptor present upon chromosome 17q21 which encrypts an intracellular proteins 185KD that lacks a normal ligand. Mitogen-activated protein kinase (MAPK) is activated byHer-2, which initiates signal cascades and phosphoinositidyl-3- kinase pathways PI3K/AKT those are essential for differentiation and proliferation of cells \unskip~\citep{988850:21274302}.

The dysregulation in the form of mutations, over expression by Her 2/neu encourages the development \& transfer of tumors \unskip~\citep{988850:21274289}. In the tumor model system, the gene of Her-2/neu overexpression avidly compares to mutagenesis, improved motility of cell, malignant transformation, metastasis and invasion. Other epithelial malignancies such as carcinoma lung, prostate and bladder have shown overexpression of Her-2/neu in several studies \unskip~\citep{988850:21274302}.

Thus, potential new adjuvant monoclonal Antibody can be used, which causes direct inhibition of Tyrosine kinase (TRK) activity resulting in proapoptotic, antiangiogenic and anti-invasive effect \unskip~\citep{988850:21274286}.

\textbf{Aim \& Objective}
  
  \begin{enumerate}
  \item \relax To study the incidence of various lesions of lower gastro-intestinal colonoscopic biopsy.
  \item \relax To study histopathology of lower GI lesions and find out the incidence of various non-neoplastic as well as neoplastic lesions.
  \item \relax To study the Her2/neu expression in carcinoma of the colon with respect to age, sex, site, type and grade.
  \end{enumerate}
  
    
\section{Materials and Methods}
A study was conducted prospectively in a tertiary care teaching hospital from July 2015 till Oct 2017, on the lower GI colonoscopic biopsies, sent from the Department of Gastroenterology of the same institution. Inclusion criteria included patients of either sex of all age groups with lower gastrointestinal signs and symptoms and visible mucosal lesions.

The exclusion criteria were patients with perforated viscus, cases with prior chemo and radiotherapy and recent history of myocardial infarction. All histologically confirmed cases of CRC were included for Her2neu study with a follow-up of one year. After obtaining the well informed consent and thorough health experience, endoscopy with a compact forward facing camera endoscope \& five to eight colonoscopies from the different quadrant of the surface and margins of the mucosal lesions. All clinico-radiologic and endoscopic reports were procured for subsequent histopathologic examination. Full thickness biopsy of mucosa without much submucosal tissue was obtained from the margin (all four quadrants) surface and surrounding mucosa of suspicious lesions, as well as 4-6 biopsy from different segments of the colon, were taken. Tissue processing was followed by Harris Hematoxylin and eosin (H \& E) staining followed by special staining was done, for establishing a final diagnosis. All cases of the CRC were subjected to IHC stain of Her2neu using DAKO polyclonal rabbit anti-human cerb-2 oncoprotein. Patients, especially with IHC of Her-2/neu, score 2+ tumors, were enrolled with fluorescent in-situ hybridization (FISH) testing.

\textbf{Procedure}

IHC is a method based on Antigen-Antibody reaction for identifying antigenic substance in the tissue. The primary Antibody binds to specific tissue antigens. The biotinylated secondary Antibody is directed to primary Antibody. The streptavidin/horseradish peroxidase complex is then applied. Streptavidin then binds to biotin on the secondary antibody and Horseradish peroxidase (HRP) acts as an indicator enzyme. On addition of diaminobenzidine (DAB) substrate, free oxygen radicals are released which oxidize DAB to brown precipitation. The precipitate gets deposited on the antigen site and can be detected by microscopy \unskip~\citep{988850:21274283}.

The four tier scoring system used by \unskip~\cite{988850:21274296}, for Her2 expression in gastric carcinoma, was used in our study for scoring Her2/neu of all the colorectal carcinoma Table~\ref{tw-c1a193bcd8fd}.

\textbf{Observation}

In this study, the wide age range was covered from


\begin{table*}[!htbp]
\caption{\boldmath {Guideline for colorectal carcinoma test of Her-2/neu} }
\label{tw-c1a193bcd8fd}
\def\arraystretch{1.1}
\ignorespaces 
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\begin{tabulary}{\linewidth}{p{\dimexpr.15919999999999998\linewidth-2\tabcolsep}p{\dimexpr.667\linewidth-2\tabcolsep}p{\dimexpr.17379999999999995\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Score & Observation & \cAlignHack Staining \\
\tblmidrule 
\cAlignHack 0 &
  No sign of cell staining in \textless\ 12 percent &
  \cAlignHack Negative\\
\cAlignHack One+ &
  Light, scarcely noticeable in {\textgreater} 12 per cent of the cells; &
  \cAlignHack Negative\\
\cAlignHack Two+ &
  In {\textgreater} 12 percent of cells, low to medium staining; circumferential, basolateral or lateral. &
  \cAlignHack Equivocal \\
\cAlignHack Three+ &
  Stressful in {\textgreater} 12\% of the cell; transverse, horizontal, or basolateral. &
  \cAlignHack Positive\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Histopathology findings in the various lesion of the lower gastrointestinal tract} }
\label{tw-c3eed54a81eb}
\def\arraystretch{1.1}
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\begin{tabulary}{\linewidth}{p{\dimexpr.7300999999999999\linewidth-2\tabcolsep}p{\dimexpr.16570000000000004\linewidth-2\tabcolsep}p{\dimexpr.10419999999999998\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}HPS & \cAlignHack No of pts & \cAlignHack \%\\
\tblmidrule 
Non-specific ileitis &
  \cAlignHack 14 &
  \cAlignHack 5.40\\
Other-Melanosis coli, infective, pseudomembranous colitis,  &
  \cAlignHack 8 &
  \cAlignHack 3.12\\
Idiopathic Bowel Disease (Acute colitis, Chronic Active, chronic inactive, indeterminate UC, and Crohn's disease)  &
  \cAlignHack 55 &
  \cAlignHack 21.48\\
Intestinal tuberculosis, Solitary Rectal syndrome, Proctitis, Fistula in ano &
  \cAlignHack 36 &
  \cAlignHack 14.06\\
Colorectal polyp &
  \cAlignHack 38 &
  \cAlignHack 14.84\\
Adenomas &
  \cAlignHack 15 &
  \cAlignHack 5.85\\
Colorectal carcinomas &
  \cAlignHack 90 &
  \cAlignHack 35.15\\
Total  &
  \cAlignHack 256 &
  \cAlignHack 100.00\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
2 years to 85 years with a maximum number of patients who underwent colonoscopy belonged to 41 {\textendash} 60 years of the age group in both sexes. Sex ratio is 1.4:1, male (58.88\%) and female (41.11\%). The incidence of disease was more commonly found in the rectum (43.7\%) in comparison to other sites of the lower GI tract. Out of 256 cases, the number of patients suffering from colorectal carcinoma was 35.15\%, followed by IBD 21.48\%, non-neoplastic polyp 14.84 \% and neoplastic polyp 5.85\%. Among 55 cases of idiopathic collative ulcers, inflammatory bowel syndrome was 19.6\%, disease of Crohn was only 3.4\% revealed different stages of colitis (acute, chronic acute and inactive) together constitute 21.48\%. The incidence of Inflammatory polyp (39.47\%) is highest among the group of non-neoplastic polyps Table~\ref{tw-c3eed54a81eb}. 


\bgroup
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\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/5951f955-378e-4f07-a61e-c6680712d0c9-upicture1.png}{\includegraphics{images/5951f955-378e-4f07-a61e-c6680712d0c9-upicture1.png}}{}
\makeatother 
\caption{\boldmath {1a. showing tubullovillous adenoma with high grade dysplasia (100x), 1b. showing nuclear crowding and hyperchromasia (400x)}}
\label{f-6969451c02be}
\end{figure}
\egroup
Adenomas are localized in the rectum (46.67\%) followed by a sigmoid colon (26.6\%). Tubular adenomas constituted 80.0\% Figure~\ref{f-6969451c02be}. Tubulovillous adenoma comprised 13.33\%and villous adenoma is least with 6.67\%. The distribution of adenoma, according to a different site, is depicted in Table~\ref{tw-9cf516c67ba6}. Age sex distribution of colon carcinomas is given in Table~\ref{tw-5beadddca39e}.

The different subtypes of CRC included were adenocarcinoma {\textendash} NOS (64.44\%) followed by mucinous signet ring type, basaloid and adenosquamous type. The Histopathological spectrum of carcinoma as per site and type are depicted in Table~\ref{tw-5cac430abc07}. The distribution of Her2 scoring according to the site of lesion is provided in Table~\ref{tw-24ef55d78e17} and Her2/neu scoring according to Histopathological type, are given in Table~\ref{tw-6ee3c6f291ee}.


\bgroup
\fixFloatSize{images/035d7e3a-84dc-4a07-9681-358af67e9c05-upicture2.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/035d7e3a-84dc-4a07-9681-358af67e9c05-upicture2.png}{\includegraphics{images/035d7e3a-84dc-4a07-9681-358af67e9c05-upicture2.png}}{}
\makeatother 
\caption{\boldmath {2a. showing moderately diffentiated adenocarcinoma NOS, (100x), 2b. showing Her2 neu score 3+, intense circumferential membrane staining in {\textgreater}10\% of cells (100x)}}
\label{f-998c39beac23}
\end{figure}
\egroup

\begin{table*}[!htbp]
\caption{\boldmath {Distribution of Types of Adenomas (Neoplastic polyps) large intestine (n=15)} }
\label{tw-9cf516c67ba6}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.2357\linewidth-2\tabcolsep}p{\dimexpr.1131\linewidth-2\tabcolsep}p{\dimexpr.1009\linewidth-2\tabcolsep}p{\dimexpr.09410000000000002\linewidth-2\tabcolsep}p{\dimexpr.09310000000000002\linewidth-2\tabcolsep}p{\dimexpr.09799999999999999\linewidth-2\tabcolsep}p{\dimexpr.084\linewidth-2\tabcolsep}p{\dimexpr.1001\linewidth-2\tabcolsep}p{\dimexpr.081\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Region of large bowel & \multicolumn{2}{p{\dimexpr(.214\linewidth-2\tabcolsep)}}{\cAlignHack Tubullovillous} & \multicolumn{2}{p{\dimexpr(.18720000000000006\linewidth-2\tabcolsep)}}{\cAlignHack Tubular} & \multicolumn{2}{p{\dimexpr(.182\linewidth-2\tabcolsep)}}{\cAlignHack Villous} & \multicolumn{2}{p{\dimexpr(.1811\linewidth-2\tabcolsep)}}{\cAlignHack Total}\\
\rowcolor{kwdboxcolor} & \cAlignHack Nos. & \cAlignHack \% & \cAlignHack Nos. & \cAlignHack \% & \cAlignHack Nos. & \cAlignHack \% & \cAlignHack Nos. & \cAlignHack \%\\
\tblmidrule 
Rectum &
  \cAlignHack 1 &
  \cAlignHack 6.67 &
  \cAlignHack 5 &
  \cAlignHack 33.33 &
  \cAlignHack 1 &
  \cAlignHack 6.67 &
  \cAlignHack 7 &
  \cAlignHack 46.67\\
Sigmoid colon &
  \cAlignHack 1 &
  \cAlignHack 6.67 &
  \cAlignHack 3 &
  \cAlignHack 20 &
  \cAlignHack 0 &
  \cAlignHack - &
  \cAlignHack 4 &
  \cAlignHack 26.67\\
Descending colon &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack -\\
Transverse colon &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack 1 &
  \cAlignHack 6.67 &
  \cAlignHack 0 &
  \cAlignHack - &
  \cAlignHack 1 &
  \cAlignHack 6.67\\
Right colon &
  \cAlignHack 0 &
  \cAlignHack - &
  \cAlignHack 3 &
  \cAlignHack 20 &
  \cAlignHack 0 &
  \cAlignHack - &
  \cAlignHack 3 &
  \cAlignHack 20.00\\
Total &
  \cAlignHack 2 &
  \cAlignHack 13.33 &
  \cAlignHack 12 &
  \cAlignHack 80 &
  \cAlignHack 1 &
  \cAlignHack 6.67 &
  \cAlignHack 15 &
  \cAlignHack 100.00\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Age and sex distribution of cancer colon in accordance to site (n=90)} }
\label{tw-5beadddca39e}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.13\linewidth-2\tabcolsep}p{\dimexpr.09900000000000002\linewidth-2\tabcolsep}p{\dimexpr.10099999999999998\linewidth-2\tabcolsep}p{\dimexpr.11\linewidth-2\tabcolsep}p{\dimexpr.11\linewidth-2\tabcolsep}p{\dimexpr.119\linewidth-2\tabcolsep}p{\dimexpr.114\linewidth-2\tabcolsep}p{\dimexpr.1279\linewidth-2\tabcolsep}p{\dimexpr.0891\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Age group & \multicolumn{4}{p{\dimexpr(.42\linewidth-2\tabcolsep)}}{\cAlignHack Colon} & \multicolumn{4}{p{\dimexpr(.45\linewidth-2\tabcolsep)}}{\cAlignHack Rectum}\\
\rowcolor{kwdboxcolor}\cAlignHack  & \cAlignHack Male & \cAlignHack \% & \cAlignHack Female & \cAlignHack \% & \cAlignHack Male & \cAlignHack \% & \cAlignHack Female & \cAlignHack \%\\
\tblmidrule 
\cAlignHack 0-20 &
  \cAlignHack 0 &
  \cAlignHack - &
  \cAlignHack 0 &
  \cAlignHack - &
  \cAlignHack 1 &
  \cAlignHack 1.11 &
  \cAlignHack 0 &
  \cAlignHack -\\
\cAlignHack 21-40 &
  \cAlignHack 3 &
  \cAlignHack 3.33 &
  \cAlignHack 4 &
  \cAlignHack 4.44 &
  \cAlignHack 4 &
  \cAlignHack 4.44 &
  \cAlignHack 7 &
  \cAlignHack 7.77\\
\cAlignHack 41-50 &
  \cAlignHack 4 &
  \cAlignHack 4.44 &
  \cAlignHack 2 &
  \cAlignHack 2.22 &
  \cAlignHack 2 &
  \cAlignHack 2.22 &
  \cAlignHack 6 &
  \cAlignHack 6.66\\
\cAlignHack 51-60 &
  \cAlignHack 11 &
  \cAlignHack 12.22 &
  \cAlignHack 2 &
  \cAlignHack 2.22 &
  \cAlignHack 7 &
  \cAlignHack 7.77 &
  \cAlignHack 5 &
  \cAlignHack 5.55\\
\cAlignHack 61-70 &
  \cAlignHack 3 &
  \cAlignHack 3.33 &
  \cAlignHack 4 &
  \cAlignHack 4.44 &
  \cAlignHack 10 &
  \cAlignHack 11.11 &
  \cAlignHack 2 &
  \cAlignHack 2.22\\
\cAlignHack {\textgreater}71 &
  \cAlignHack 4 &
  \cAlignHack 4.44 &
  \cAlignHack 1 &
  \cAlignHack 1.11 &
  \cAlignHack 4 &
  \cAlignHack 4.44 &
  \cAlignHack 4 &
  \cAlignHack 4.44\\
\cAlignHack Total  &
  \cAlignHack 25 &
  \cAlignHack 27.77 &
  \cAlignHack 13 &
  \cAlignHack 14.44 &
  \cAlignHack 28 &
  \cAlignHack 31.33 &
  \cAlignHack 24 &
  \cAlignHack 26.66\\
\cAlignHack Mean age &
  \multicolumn{2}{p{\dimexpr(.20\linewidth-2\tabcolsep)}}{\cAlignHack 56.91} &
  \multicolumn{2}{p{\dimexpr(.22\linewidth-2\tabcolsep)}}{\cAlignHack 52.0} &
  \multicolumn{2}{p{\dimexpr(.233\linewidth-2\tabcolsep)}}{\cAlignHack 56.30} &
  \multicolumn{2}{p{\dimexpr(.217\linewidth-2\tabcolsep)}}{\cAlignHack 49.72}\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Histopathological carcinoma spectrum colon depending upon the form \& location (n=90)} }
\label{tw-5cac430abc07}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.124\linewidth-2\tabcolsep}p{\dimexpr.196\linewidth-2\tabcolsep}p{\dimexpr.1975\linewidth-2\tabcolsep}p{\dimexpr.1315\linewidth-2\tabcolsep}p{\dimexpr.2005\linewidth-2\tabcolsep}p{\dimexpr.1505\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Site & \cAlignHack Signet ring type & \cAlignHack Adocarcinoma & \cAlignHack Basaloid & \cAlignHack Adenosquamous & \cAlignHack Mucinous\\
\tblmidrule 
\cAlignHack Colon &
  \cAlignHack 2(1.11\%) &
  \cAlignHack 29(31.11\%) &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack 8(7.77\%)\\
\cAlignHack Rectum &
  \cAlignHack 6(6.66\%) &
  \cAlignHack 31(33.33\%) &
  \cAlignHack 3 (3.33\%) &
  \cAlignHack 2(2.22\%) &
  \cAlignHack 14 (14.44\%)\\
\cAlignHack Total  &
  \cAlignHack 7(7.77\%) &
  \cAlignHack 58(64.44\%) &
  \cAlignHack 3 (3.33\%) &
  \cAlignHack 2(2.22\%) &
  \cAlignHack 20 (22.22\%)\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\bgroup
\fixFloatSize{images/ad68d05f-d60b-4a1f-b2fa-2a64b5000e3b-upicture3.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/ad68d05f-d60b-4a1f-b2fa-2a64b5000e3b-upicture3.png}{\includegraphics{images/ad68d05f-d60b-4a1f-b2fa-2a64b5000e3b-upicture3.png}}{}
\makeatother 
\caption{\boldmath {3a. showing moderately differentiated adenocarcinoma NOS, (100x), 3b. showing Her2/neu rating 2+ weakened to fine staining in cells of {\textgreater}12\%c (100x)}}
\label{f-c3098c31835f}
\end{figure}
\egroup
For ninety cases reported into Her-2neu IHC, 6 cases (6.66\%) for adenomas were optimistic with a rating of 3+ Figure~\ref{f-998c39beac23}, 16 cases (17.77\%) of adenomas displaying an equi-vocal rating of 2+ Figure~\ref{f-c3098c31835f}, two cases (2.22\%) of mucinous form displayed an equi-vocal rating of 2 +., whereas 10 adeno-carcinoma cases, 5 cases (5.55\%) of mucinous carcinoma two ring form signet \& single carcinoma basaloid was score 1+ Figure~\ref{f-39240ee4fdd1}, and twenty six adeno-carcinoma cases, thirteen mucinous scenarios, three cases each of signet ring type, two cases each of basaloid, \& of adenosquamous carcinomas found -ve by rating 0.

The score 2+ positive cases were subjected to FISH study. Out of 20 cases of Her2neu 2+ score 4 (33.33\%) cases was found to be Her2neu 3+ score in the FISH study (33.3\%). Both high positive and negative score (18.88 \& 40.0\%) were found in Cancer located in the rectum. 
    
\section{Discussion}
Colonoscopy biopsy provides useful information for the diagnosis of various lesion of the lower gastrointestinal tract. In this study, 256 patients were evaluated, most of which were in the 41-60 years age group, mean age being 45 years showing male sex predominance of about 58.88\%, while females were 41.11\%.


\begin{table*}[!htbp]
\caption{\boldmath {Distribution of Her2/neu scores according to site of lesion (n-90)} }
\label{tw-24ef55d78e17}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.2364\linewidth-2\tabcolsep}p{\dimexpr.1605\linewidth-2\tabcolsep}p{\dimexpr.14389999999999999\linewidth-2\tabcolsep}p{\dimexpr.09760000000000002\linewidth-2\tabcolsep}p{\dimexpr.11949999999999998\linewidth-2\tabcolsep}p{\dimexpr.14380000000000003\linewidth-2\tabcolsep}p{\dimexpr.0983\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Expression at the location of Her2/neu  & \multicolumn{2}{p{\dimexpr(.30439999999999998\linewidth-2\tabcolsep)}}{\cAlignHack Her2/neu positive and equivocal} & \multicolumn{2}{p{\dimexpr(.2171\linewidth-2\tabcolsep)}}{\cAlignHack Her2/neu negative} & \multicolumn{2}{p{\dimexpr(.2421\linewidth-2\tabcolsep)}}{\cAlignHack Total in CRC }\\
\rowcolor{kwdboxcolor}\cAlignHack  & \cAlignHack \% & \cAlignHack N & \cAlignHack \% & \cAlignHack N & \cAlignHack \% & \cAlignHack N\\
\tblmidrule 
\cAlignHack Colon &
  \cAlignHack 10.00 &
  \cAlignHack 10 &
  \cAlignHack 31.11 &
  \cAlignHack 28 &
  \cAlignHack 41.11 &
  \cAlignHack 37.\\
\cAlignHack Rectum &
  \cAlignHack 18.88 &
  \cAlignHack 17 &
  \cAlignHack 40 &
  \cAlignHack 36 &
  \cAlignHack 58.8 &
  \cAlignHack 53\\
\cAlignHack Total  &
  \cAlignHack 28.88 &
  \cAlignHack 26 &
  \cAlignHack 71.11 &
  \cAlignHack 64 &
  \cAlignHack 100.00 &
  \cAlignHack 90\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Immunohistochemistry: Score of Her2/neu score as per Histopathological form (n = 90)} }
\label{tw-6ee3c6f291ee}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.17990000000000002\linewidth-2\tabcolsep}p{\dimexpr.07420000000000003\linewidth-2\tabcolsep}p{\dimexpr.06929999999999999\linewidth-2\tabcolsep}p{\dimexpr.06249999999999998\linewidth-2\tabcolsep}p{\dimexpr.06710000000000003\linewidth-2\tabcolsep}p{\dimexpr.07140000000000002\linewidth-2\tabcolsep}p{\dimexpr.06040000000000002\linewidth-2\tabcolsep}p{\dimexpr.06029999999999999\linewidth-2\tabcolsep}p{\dimexpr.07010000000000002\linewidth-2\tabcolsep}p{\dimexpr.09610000000000001\linewidth-2\tabcolsep}p{\dimexpr.0734\linewidth-2\tabcolsep}p{\dimexpr.05629999999999999\linewidth-2\tabcolsep}p{\dimexpr.059\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Score & \multicolumn{2}{p{\dimexpr(.14350000000000001\linewidth-2\tabcolsep)}}{\cAlignHack Adenocar \mbox{}\protect\newline cinoma} & \multicolumn{2}{p{\dimexpr(.1296\linewidth-2\tabcolsep)}}{\cAlignHack Mucinous} & \multicolumn{2}{p{\dimexpr(.13180000000000003\linewidth-2\tabcolsep)}}{\cAlignHack Signet ring type} & \multicolumn{2}{p{\dimexpr(.13040000000000001\linewidth-2\tabcolsep)}}{\cAlignHack Basaloid} & \multicolumn{2}{p{\dimexpr(.16950000000000003\linewidth-2\tabcolsep)}}{\cAlignHack Adenosquamoid} & \multicolumn{2}{p{\dimexpr(.1153\linewidth-2\tabcolsep)}}{\cAlignHack Total}\\
\rowcolor{kwdboxcolor} & \cAlignHack n & \cAlignHack \% & \cAlignHack n & \cAlignHack \% & \cAlignHack n & \cAlignHack \% & \cAlignHack n & \cAlignHack \% & \cAlignHack n & \cAlignHack \% & \cAlignHack n & \cAlignHack \%\\
\tblmidrule 
Her2/neu +ve score 3+ &
  \cAlignHack 6 &
  \cAlignHack 7.66 &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack 6 &
  \cAlignHack 7.66\\
Her2/neu equi-vocal score 2+ &
  \cAlignHack 16 &
  \cAlignHack 17.77 &
  \cAlignHack 2 &
  \cAlignHack 2.22 &
  \cAlignHack 2 &
  \cAlignHack 2.22 &
  \cAlignHack 0 &
  \cAlignHack - &
  \cAlignHack 0 &
  \cAlignHack - &
  \cAlignHack 20 &
  \cAlignHack 22.22\\
Her2/neu negative score 1+ &
  \cAlignHack 10 &
  \cAlignHack 11.11 &
  \cAlignHack 5 &
  \cAlignHack 5.55 &
  \cAlignHack 2 &
  \cAlignHack 2.22 &
  \cAlignHack 1 &
  \cAlignHack 1.11 &
  \cAlignHack 0 &
  \cAlignHack - &
  \cAlignHack 18 &
  \cAlignHack 20\\
Her2/neu negative score 0 &
  \cAlignHack 26 &
  \cAlignHack 28.88 &
  \cAlignHack 13 &
  \cAlignHack 14.44 &
  \cAlignHack 3 &
  \cAlignHack 3.33 &
  \cAlignHack 2 &
  \cAlignHack 2.22 &
  \cAlignHack 2 &
  \cAlignHack 2.22 &
  \cAlignHack 46 &
  \cAlignHack 51.01\\
Total  &
  \cAlignHack 58 &
  \cAlignHack 64.44 &
  \cAlignHack 20 &
  \cAlignHack 22.22 &
  \cAlignHack 7 &
  \cAlignHack 7.77 &
  \cAlignHack 3 &
  \cAlignHack 3.33 &
  \cAlignHack 2 &
  \cAlignHack 2.22 &
  \cAlignHack 90 &
  \cAlignHack 100.00\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
The statistics coincided with \unskip~\cite{988850:21274295} whose study reported male predominance 64\% and mean age of presentation being 48.5 yrs.


\bgroup
\fixFloatSize{images/71e5968c-2360-4eac-a30f-fa677ae0cb51-upicture4.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/71e5968c-2360-4eac-a30f-fa677ae0cb51-upicture4.png}{\includegraphics{images/71e5968c-2360-4eac-a30f-fa677ae0cb51-upicture4.png}}{}
\makeatother 
\caption{\boldmath {4a. showing signet ring cell carcinoma (100x), 4b inset showing positivity for special stain PAS, 4c. showing Her2/neu rating 1+ with light and scarcely visible granular staining in cells {\textgreater}12\% (100x)}}
\label{f-39240ee4fdd1}
\end{figure}
\egroup
Within present research, predominant abrasions are into the rectum (60.0\%) followed by pan colon (28.75\%), ascending colon and caecum (12.8\%), sigmoid colon (6.25\%) transverse colon (2.92\%) and descending colon, anus (1.25\%). This observation correlated with the study of \unskip~\cite{988850:21274301} who represented that colonic diseases were prevalent in the left side (60\%).

The incidence of different lesions constituted 35.15\% of colorectal cancer, followed by inflammatory bowel disease (21.48\%), non-neoplastic polyps (14.06\%), This is compared with the following authors: \unskip~\cite{988850:21274298} showing IBD (16.3\%), carcinoma (10\%) and proctitis (6\%) and \unskip~\cite{988850:21274299} whose study showed IBD (27\%), carcinoma (20\%) and non neoplastic polyp (16.7\%). We had a higher incidence of CRC, attributed possibly to being a referral centre for oncology in the eastern part of India.


\begin{table}[!htbp]
\caption{\boldmath {Her2/ neu over expression by different authors} }
\label{tw-08f948c15bec}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.4618\linewidth-2\tabcolsep}p{\dimexpr.5382\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Authors & \cAlignHack Her2/neu positivity (Score 3+)\\
\tblmidrule 
Present study &
  \cAlignHack 6.52\%\\
\unskip~\citep{988850:21274294} &
  \cAlignHack 10.6\%\\
\unskip~\citep{988850:21274280} &
  \cAlignHack 5\%\\
\unskip~\citep{988850:21274281} &
  \cAlignHack 4.3\%\\
\tblbottomrule 
\end{tabulary}\par 
\end{table}
Inside the class of intestinal disorder, which is inflammatory (21.48\%) out of which ulcerative colitis constituted (21.48\%) and Crohn's disease (2.4\%). The study well correlated with that of A \unskip~\cite{988850:21274290} who found ulcerative colitis (16\%), infective colitis (18.04\%) and no cases of Crohn's disease. Similarly, \unskip~\citet{988850:21274287} found Superior incidence of colitis ulcer (65\%) than the disease of Crohn (35\%).

The current study shows the incidence of non-neoplastic colorectal polyps constituted 14.84\% of total cases out of which, inflammatory polyp (39.47\%), the juvenile polyp was (31.57\%), hyperplastic polyp (23.68\%) and least was hamartomatous polyp (5.26\%). Adenoma (neoplastic polyps) constituted about 6.0\% of total cases of which, tubular adenoma was (80\%), tubulovillous adenoma (13.33\%) and villous adenoma (6.67\%). The commonest location of adenoma was rectum (47\%) followed by a sigmoid colon (27\%) showing male predominance. In the study of \unskip~\cite{988850:21274291} stated that malignant polyps were low compared to non-neoplastic polyp of which hyperplastic polyps were commonest (23.22\%) and tubullovillous adenoma was 8.11\%. The study by \unskip~\citep{988850:21274298} also found that hyperplastic polyps were commonest and tubular adenoma commonest amongst neoplastic polyps (16.3\%).

Colorectal carcinoma constituted 35.15\% majority of which located in the rectum (55.55\%). The age incidence ({\textgreater}50 years), was similar to \unskip~\cite{988850:21274297} While cancers of colorectal have reported to be two times higher in males as compared with the female and median age being 50 years. CRC in the current study was mostly adenocarcinoma NOS type (64.44\%) that correlated with \unskip~\cite{988850:21274284}  showing 98\% of colon cancer to be adenocarcinoma, NOS type.

The Her2/neu expression was more found in left sided colon compared to right sided colon. Strong Her2neu (score 3+) was found in 6.66\% cases which were moderately differentiated adenocarcinoma. Score 2+ was observed in \unskip~\cite{988850:21274280}. 22\% of colorectal carcinoma out of which 33.3\% were found to be score 3+ on the FISH study, were found mostly in high grade colon adenocarcinoma. The subtypes of adenocarcinoma like mucinous, signet ring type, cloacogenic and adenosquamous type showed negative score for Her2neu. The percentage of positivity of Her2neu in CRC was well correlated with other authors given in Table~\ref{tw-08f948c15bec}.
    
\section{Conclusions}
Commonest type of CRC was adenocarcinoma (NOS) followed by mucinous, adenosquamous, basaloid \& signet ring form. Because of more prominent membranous staining observed in high grade colorectal cancers like breast carcinoma, Her2neu expression is found to be an important predictive marker of carcinoma colon. Thus, in a nutshell, this study concludes that both conventional as non-conventional adenocarcinoma among colorectal Cancer especially those by lymphovascular inflation metastasis, Her-2 / new expression must be evaluated in the form of a different therapeutic approach, due to many stained membranes in higher grades of CRC (grade II, grade III). Treatment of Herceptin may assists individuals suffering from disease, especially in adenocarcinoma, NOS category. Other poorly differentiated carcinoma (grade III) like mucinous and signet ring cell type do not well respond to Herceptin therapy.

\textbf{Conflict of Interest}

The authors declare that they have no conflict of interest for this study.

\textbf{Funding Support}

The authors declare that they have no funding support for this study.
    

\bibliographystyle{pharmascope_apa-custom}

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\end{document}
